AU2009226063A1

AU2009226063A1 - Blocking the metastasis of cancer cells and the uses of new compounds thereof

Info

Publication number: AU2009226063A1
Application number: AU2009226063A
Authority: AU
Inventors: Pui-Kwong Chan; May Sung Mak
Original assignee: Pacific Arrow Ltd
Current assignee: Pacific Arrow Ltd
Priority date: 2008-02-15
Filing date: 2009-02-13
Publication date: 2009-09-24
Also published as: WO2009117196A8; EP2254899A4; WO2009117196A1; EP2254899A1; CN101998964A; CN101998964B; CA2715501A1

Description

WO 2009/117196 PCT/US2009/034115 1 INTERNATIONAL PATENT APPLICATION UNDER THE PATENT COOPERATION TREATY To all whom it may concern: Be it known that Pui-Kwong CHAN and May Sung MAK have invented certain new and useful improvements in BLOCKING THE METASTASIS OF CANCER CELLS AND THE USES OF NEW COMPOUNDS THEREOF of which the following is a full, clear and exact description.

WO 2009/117196 PCT/US2009/034115 2 BLOCKING THE METASTASIS OF CANCER CELLS AND THE USES OF NEW COMPOUNDS THEREOF This application claims benefit of U.S. Serial No. 61/038,277 filed March 20, 2008, U.S. 5 Serial No. 61/054,308, filed May 19, 2008, International App'l No. PCT/US2008/002086, filed February 15, 2008, International App'l No. PCT/US2007/077273, filed August 30, 2007, U.S. Serial No. 60/890,380, filed on February 16, 2007, U.S. No. 60/947,705, filed on July 3, 2007, and U.S. Serial No.11/683,198, filed on March 7, 2007, which claims benefit of U.S. Serial Nos. 60/795,417, filed on April 27, 2006, 60/841,727, filed on 10 September 1, 2006, 60/890,380, filed on February 16, 2007, and International Application No. PCT/US2006/016158, filed April 27, 2006, which claims the benefit of the priority of the following applications: (1) U.S. Serial Nos. 11/289142, filed November 28, 2005, and 11/267,523, filed November 4, 2005; (2) International Application No. PCT/US05/31900, filed September 7, 2005 (which claims the priority of U.S. Serial Nos. 15 60/617,379, filed October 8, 2004, 60/613,811, filed September 27, 2004, and 60/607,858, filed September 7, 2004); (3) U.S. Serial No. 11/131,551, filed May 17, 2005; and (4) U.S. Serial No. 11/117,760, filed April 27, 2005. This application also claims benefit of U.S. Serial No.11/412,659, filed April 27, 2006, U.S. Serial No. 10/906,303, filed February 14, 2005, and U.S. Serial No. 12/344,682, filed December 29, 20 2008. The contents of these preceding applications are hereby incorporated in their entireties by reference into this application. FIELD OF THE INVENTION This invention provides methods and compositions for reducing the adhesion protein in 25 cell and blocks the migration, metastasis of cancer cells or inhibits the growth of cancers or anti-angiogenesis; wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancers, wherein the adhesion proteins or receptors comprise fibronectin, integrins 30 family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. BACKGROUND OF THE INVENTION The composition from Maesa balansae for anti-leishmanial is a United Nation funding 35 project. This invention is providing methods for inhibiting cancer metastasis or growth, wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, WO 2009/117196 PCT/US2009/034115 3 spleen, kidney, lymph, pancreas, stomach and thyroid cancers, wherein the method is using the extract, composition and compounds from Maesa balansae, Barringtonia acutangula, Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum. 5 SUMMARY OF THE INVENTION This invention is providing methods of using the extract, composition and compounds from Maesa balansae and Barringtonia acutangula, Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum for reducing adhesion protein, for inhibiting cancer metastasis, wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, 10 bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancers. This invention provides a method for modulating the adhesion of cancer cell and blocking their migration, metastasis or inhibiting the growth of cancers or anti 15 angiogenesis, wherein the adhesion protein and their receptors comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. This invention provides a method of antiprotozoal comprising treating leishmaniases, 20 amoebiasis, trypanosomiasis, toxoplasmosis and malaria.

WO 2009/117196 PCT/US2009/034115 4 DETAILED DESCRIPTION OF THE FIGURES Figure 1: Analysis of genesis of blood vessel in xenograft tumor treated with compound Y. Figure A and B show the tumor sections taking from mice without 5 Xanifolia Y treatment. Figure C and B show the tumor sections taking from mice with Xanifolia Y treatment. More blood vessels were observed in the control Group1 than those in the drug-treated Group 2 Figure 2: Experiment shows that Y1 0 is cytotoxic to Leishmania Major (promastigotes) 10 with IC50 approximately equal to 15ug/ml. Figure 3: Shows the inhibition activity of compound Y, X, ACH-Y and AKOH-Y WO 2009/117196 PCT/US2009/034115 5 DETAILED DESCRIPTION OF THE INVENTION This invention provides methods and compositions for modulating the gene expression to cure diseases or reduce the syndrome of diseases, wherein the modulating comprises positive and negative regulating. In an embodiment, the method comprises 5 inhibiting the gene expression. In an embodiment the method comprises stimulating the gene expression. This invention provides methods and compositions for inhibiting the migration, metastasis or growth of cancers or anti-angiogenesis, wherein the methods comprise 10 affecting the gene expression, wherein comprise affecting the adhesion proteins or their receptors, reducing adhesion protien, or inhibiting the expression or secretion of adhesion proteins, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin , vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. 15 This invention provides methods and compositions for inhibiting the migration, metastasis or growth of cancers or anti-angiogenesis, wherein the methods comprise affecting the gene expression, wherein comprises stimulating the gene expression. 20 This invention provides a method for altering the characteristic of cancer cell membrane resulting in blocking the migration, metastasis of cancer cells or inhibit the growth of cancers or anti-angiogenesis, wherein the method comprises reducing adhesion protiens or their receptors, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface 25 proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. This invention provides methods, processes, compounds and compositions of reducing adhesion protein of cells, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, 30 polyglycans, cadherin, heparin, tenascin, CD54, CAM, elastin and FAK. In an embodiment, methods comprise inhibiting the gene expression. In an embodiment, this invention provides a method of reducing the secretion of fibronectin. In an embodiment the method can block the migration, metastasis of cancer cells or inhibit the growth of cancers or anti-angiogenesis, wherein the cancers comprise breast, leukocyte, liver, 35 ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid WO 2009/117196 PCT/US2009/034115 6 cancer. In an embodiment, the method is contracting the said cell with compound selected from Mbl, Mb2, Mb2.1, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, Mbl0, Mbl1, Mb12 and Mb13, ACH-Z4, ACH-Y1O, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, Bal, Ba2, Ba3, Ba4, Ba5, Ba6, Ba7, Ba8, Ba9, Bal0, Bal1, Bal2, Bal3, Bal4, 5 Bal 5, Bal 6, Bal 7, Xanifolia YO, Y1, Y2, Y, Y5, Y7, Y8, Y9, Y1 0, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof and Compound A to X and Al to X1 in the application. This invention provides a method of altering the characteristic of cancer cell membrane, 10 wherein the method comprises altering the secretion of adhesion proteins, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. In an embodiment, the methods, processes, compounds and compositions comprises blocking, suppressing or inhibiting the expression or 15 secretion of adhesion protein, wherein the adhesion proteins . In an embodiment, the methods, processes, compounds and compositions is interacting with adhesion protein, wherein the adhesion proteins. In an embodiment the methods, processes, compounds or compositions can block the migration, metastasis of cancer cells or inhibit the growth of cancers or anti-angiogenesis, wherein the cancers comprise breast, leukocyte, liver, 20 ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancer. In an embodiment, the method is contracting the said cell with compound selected from Mbl, Mb2, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, MblO, Mbll, Mb12 and Mbl3,, ACH-Z4, ACH-Y1O, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, 25 Bal, Ba2, Ba3, Ba4, Ba5, Ba6, Ba7, BaB, Ba9, Bal0, Bal1, Bal2, Bal3, Bal4, Ba15, Bal 6, Ba 17, Xanifolia YO, Y1, Y2, Y, Y7, Y8, Y9, Y1 0, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof and Compound A to X and Al to X1 in the application. The adhesion proteins help cancer cell adhesion, invasion or metastasis, wherein the 30 cancers comprise ovarian cancer. Reducing the adhesion proteins will reduces the metastasis of cancers.The fibronectin is one of the key factors in the biology of epithelial ovarian cancers. The reducing of fibronectin will inhibit the metastasis of cancer cells. This invention provides a method and composition for inhibiting the secretion of adhesion protein comprising fibronectin in order to cure the diseases, wherein the 35 diseases comprise inhibiting cancer growth, wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, WO 2009/117196 PCT/US2009/034115 7 CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancer. In an embodiment, the method is contracting the said cell with compound selected from Mbl, Mb2, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, MblO, Mb11, Mb12 and Mb13, ACH-Z4, ACH-Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, 5 ACH-X, ACH-E, ACH-Mb5, ACH-Mbl3, Bal, Ba2, Ba3, Ba4, Ba5, Ba6, Ba7, Ba8, Ba9, Bal0, Bal1, Bal2, Bal3, Bal4, Bal5, Bal6, Ba 17, Xanifolia YO, Y1, Y2, Y, Y7, Y8, Y9, Y10, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof and Compound A to X and Al to X1 in the application. 10 This invention provides a use of compound for manufacture of medicament or a composition for inhibiting the growth, migration, metastasis of cancer and by altering the characteristics of membrane of cancer cell, wherein the characteristics comprise adhesion of proteins; wherein comprising the secretion of proteins or the adhesion of cells; wherein the characteristic comprise adhesion ability; wherein the adhesion 15 proteins comprise fibronectin, integrins family, Myosin , vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK; wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancer; 20 wherein the method is administering contacting the say cells with the extract, compositions, saponins and compounds from Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae and Barringtonia acutangula for inhibiting cancer metastasis, wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, 25 cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancers; wherein extracts, compositions, saponins and compounds are prepared from the husks, branches, stems, leaves, kernels, roots, barks, fruit, seeds or seed shells of the herb or plant. 30 The present invention provides vaccine for cancer immunotherapy. The vaccines comprise extract, compositions, compounds and saponins from Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae and/or Barringtonia acutangula. In embodiment, the compounds can be obtained from synthesis, semi-synthesis or modification. The method comprises administering to the said subject and effective 35 amount of vaccine for enhancing the immune response. The vaccines comprise WO 2009/117196 PCT/US2009/034115 8 saponins isolated from Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae and/or Barringtonia acutangula. The present invention provides adjuvant compositions for cancer curing. The adjuvant 5 compositions comprise extract, compositions, compounds and saponins from Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae and/or Barringtonia acutangula. The method comprises administering to the said subject and effective amount of the above adjuvant compositions for enhancing the immune response. The use of vaccine compositions comprise inhibiting cancer metastasis, 10 wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancers. The present invention provide a use of compound for manufacture of medicament or 15 methods for making vaccine, wherein the vaccine comprise compounds or saponins from Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae and/or Barringtonia acutangula, wherein the vaccine can be used for inhibiting cancer growth, wherein the vaccine is having immune adjuvant activity, wherein the saponins comprise Xanifolia YO, Y1, Y2, Y, Y5, Y7, Y8, Y9, Y1 0, Xanifolia (x), Escin or Aescin or 20 a salt, ester, metabolite thereof. In an embodiment the saponin may be selected from formulas (1 A), (1 B), (1C), (1 D), (1 E), (1 F), (1 G), (1 H), (1 J), (1 K), (1 L). In an embodiment the compound(s) are selected from Compound Z1 to Z13 in the application. In an embodiment the saponin comprise Mbl, Mb2, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, MblO, Mbll, Mbl2 and Mbl3,. In an embodiment, the compound comprises a 25 triterpene backbone, two angeloyl groups and sugar moiety. In an embodiment the compound(s) are selected from Compound A to X and Al to Xl in the application. In an embodiment the compound(s) are selected from ACH-Z4, ACH-Yl 0, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, ACH-Mb5, and ACH-Mbl2. In an embodiment the saponins comprise Ba1, Ba2, Ba3, Ba4, Ba5, Ba6, Ba7, Ba8, Ba9, Ba10, Ball, Ba12, 30 Bal3, Bal4, Bal5, Bal6 and Ba 17. In an embodiment the compound(s) are selected from Xanifolia YO, Yl, Y2, Y, Y5, Y7, Y8, Y9, Yl 0, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof. In an embodiment, this invention provides a method for antiparasitics by using the above compounds, wherein the antiparasitics comprise inhibiting leishmaniases, amoebiasis, trypanosomiasis, toxoplasmosis or malaria; 35 wherein a method comprises contacting cells with an effective amount of an isolated, WO 2009/117196 PCT/US2009/034115 9 purified or synthesized compound, or its salt, or ester thereof, selected from the above compounds. This invention provides a use of compound for manufacture of medicament or a method 5 for pharmaceutical composition useful for inducing an immune response to and antigen in an individual comprising the saponin composition from Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae or Barringtonia acutangula or synthesis. The present invention provide methods for enhancing an immune response to an antigen in an individual comprising administering an effective amount of 10 saponins/compositions from Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae and/or Barringtonia acutangula, or the saponin comprise Xanifolia YO, Y1, Y2, Y, Y5, Y7, Y8, Y9, Y1 0, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof, or the saponin may be selected from formulas (1 A), (1 B), (1C), (1 D), (1 E), (1 F), (1G), (1H), (1J), (1K), (1L). In an embodiment the compound(s) are selected from 15 Compound Z1 to Z13 in the application. In an embodiment the saponin comprise Mbl, Mb2, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, Mbl0, Mbl1, Mbl2 and Mbl3, In an embodiment the compound(s) are selected from Compound A to X and Al to X1 in the application. In an embodiment the composition(s) are selected from ACH-Z4, ACH-Y1O, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, ACH-Mb5, and ACH-Mb12. In an 20 embodiment the saponins comprise Ba1, Ba2, Ba3, Ba4, Ba5, Ba6, Ba7, Ba8, Ba9, Bal0, Bal1, Bal2, Bal3, Bal4, Bal5, Bal6, Bal7. This invention is providing methods or a use of compound for manufacture of medicament for modulating adhesion or angiogenesis of cancer cells, antiparasitics, 25 enhancing an immune response, providing adjuvant activities or providing vaccine activities, inhibiting cancer metastasis or growth, of using the extract, composition and compounds from Maesa balansae, wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach 30 and thyroid cancers; In an embodiment the method is modulating the phosphatidylinositol signaling system, regulate the gene expression of RGS4 , LEPR, ICFBP3, ANGPT2, GPNMB, NUPR1 or LOC100126784. The compounds can be purified from natural resource comprising Xanthoceras Sorbifolia, Harpullia, Aesculus hippocastanum, Maesa balansae or Barringtonia acutangula, or synthesized. The 35 compounds comprise following: WO 2009/117196 PCT/US2009/034115 10 (Our purification methods and biological assays including the MTT assay in International Application No. PCT/US05/31900, filed September 7, 2005, U.S. Serial No. 11/289142, filed November 28, 2005, and U.S. Serial No. 11/131551, filed May 17, 2005, and PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008, the contents of which 5 are incorporated herein by reference) 0 OH HO 0 COOH OH 00 OHHO HOO HO HO 0 0H OH HO OH wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is (E) O(C=O)CH=CH-C6H5, R3 is OH, R4 is OH, also named Mbl; or wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is (Z) O(C=O)CH=CH-C6H5, R3 is OH, R4 is OH, also named Mb2; or wherein R1 is 10 O(C=O)C(CH3)=CH(CH3), R2 is (Z)-O(C=O)C(CH3)=CH-C6H5, R3 is OH, R4 is OH, also named Mb2.1; or wherein R1 is O(C=O)C6H5, R2 is (E)-O(C=O)CH=CH-C6H5, R3 is OH, R4 is OH, also named Mb3; or wherein R1 is O(C=O)C6H5, R2 is (Z) O(C=O)CH=CH-C6H5, R3 is OH, R4 is OH, also named Mb4; or wherein R1, R2, are O(C=O)C(CH3)=CH(CH3), R3 is OH, R4 is OH, also named Mb5; or wherein R1 is 15 O(C=O)C6H5, R2 is O(C=O)C(CH3)=CH(CH3), R3 and R4 are OH, also named Mb6; or R~ R R ~R R, HO 0 0 R 1 3 E OH 00 R, 7HO OR, ~HO O H HO OH O 0 )O HO OH wherein R1 is O(C=O)C6H5, R2 is O(C=O)CH=CH-C6H5, R3, R4, R5 are OH, R6, R7,R8, R9, R10, R11, R12 are CH3, R13 is COOH also named Mb7; or wherein R1 is 20 O(C=O)C6H5, R2 is O(C=O)CH=CH-C6H5, R3, R4, R5 are OH, R6 is CH2OH, R7, R8, R9, R10, R11, R12 are CH3, R13 is COOH also named Mb8; or wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is O(C=O)CH=CH-C6H5, R3, R4 are OH, R6, R7, R8, R9, R10, R11, R12 are CH3, R13 is COOH also named Mb9; or wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is O(C=O)CH=CH-C6H5, R3, R4 are OH, R6 is CH2OH, WO 2009/117196 PCT/US2009/034115 11 R7, R8, R9, R10, R1 1, R1 2 are CH3, R1 3 is COOH, also named Mbi 0; or wherein R1, R2, are O(C=0)C(CH3)=CH(CH3), R3 is OH, R4 is CH2OH, R5 is H, R6, R7, R8, R9, R10, R11, R12 are CH3, R13 is COOH, also named Mbl1; or wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is O(C=O)CH=CH-C6H5, R3, R4 are OH, R6, R7, R8, 5 R9, R10, R1 1, R1 2 are CH3, R1 3 is COOCH3, also named Mbl 2; or wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is (Z)-O(C=O)C(CH3)=CH-C6H5, R3 is OH, R4 is OH, R5 is H, and R6, R7, R8, R9, R10, R11, R12 are CH3, R13 is COOH, also named Mbi3; or H c 3/29 CH, 0 C OH COOH 27 HO HO OH OH 0 HO 10 OH 3-0-[j-D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1->3)-P-D-glucuronopyranosyl 21-0-angeloyl, 22-0-angeloyl-3p, 15a, 21p, 22a, 28-pentahydroxyolean-12-ene, named Ba 1 R, CH2OH OH R, , OH c 0 HO HO OH HOOH 0 HO 0 OH) OH 15 wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is O(C=O)C(CH3)=CH(CH3), R3 is COOCH3, formula is 3-0-[p-D-galactopyranosyl(1 ->2)]-p- D-xylopyranosyl (1 ->3)-p-D methylglucuronopyranosyl-21 -0-angeloyl, 22-0-angeloyl-3p, 15ca, 21 P, 22c, 28 pentahydroxyolean-1 2-ene, named Ba 2; or wherein R1 is O(C=O)C6H5, R2 is O(C=O)C(CH3)=CH(CH3), R3 is COOH, formula is: 3-0-[P-D-galactopyranosyl(1->2)] 20 f- D-xylopyranosyl (1 ->3)--D-glucuronopyranosyl-21 -0-benzoyl, 22-0-angeloyl-3p, 15a, 21p , 22a, 28-pentahydroxyolean-1 2-ene, named Ba 3; or wherein R1 is O(C=O)C6H5, R2 is O(C=O)C(CH3)=CH(CH3), R3 is COOCH3, formula is: 3-0-[p-D galactopyranosyl(1 ->2)]-p- D-xylopyranosyl (1 ->3)-p-D-methylglucuronopyranosyl-21 -0 benzoyl, 22-0-angeloyl-3p, 15ca, 21 P, 22ca, 28-pentahydroxyolean-1 2-ene, named Ba 4; 25 or wherein R1 is O(C=O)C6H5, R2 is O(C=O)C6H5, R3 is COOH, formula is: WO 2009/117196 PCT/US2009/034115 12 3-0-[ -D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1 -3)-P-D-glucuronopyranosyl 21-0-benzoyl, 22-0-benzoyl-3s, 15c, 21s, 22a, 28-pentahydroxyolean-12-ene, named Ba 5; or wherein R1 is O(C=O)C6H5, R2 is O(C=O)C6H5, R3 is COOCH3, formula is: 3-0-[s-D-galactopyranosyl(1 ->2)]-s- D-xylopyranosyl (1 -*3)-s-D 5 methylglucuronopyranosyl-21 -0-benzoyl, 22-O-benzoyl-3s, 15a, 21 s, 22a, 28 pentahydroxyolean-1 2-ene, named Ba 6; or wherein R1 is O(C=O)C6H5, R2 is O(C=O)CH3CH3, R3 is COOH, formula is: 3-O-[p-D-galactopyranosyl(1 ->2)]-p- D-xylopyranosyl (1 -*3)-s-D-glucuronopyranosyl 21 -0-benzoyl, 22-0-isobutyryl-3p, 15a, 21 P, 22a, 28-pentahydroxyolean-1 2-ene, 10 named Ba 7; or wherein R1 is O(C=O)C6H5, R2 is OH, R3 is COOH, formula is: 3-0-[ -D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1 -3)-p-D-glucuronopyranosyl 21-0-benzoyl -3s, 15ax, 21 s, 22o, 28-pentahydroxyolean-1 2-ene, named Ba 8 22 29 2HCH2OH OHH COOH27 'O HO OH 15 wherein R1 is OH , R2 is O-benzoyl, R3 is O-benzoyl, 3-0-[ -D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1 -3)-p-D-glucuronopyranosyl 21 -0-[3,4-dibenzoyl--sP-D-xylopyranosyl]- 3p, 15c, 21 s, 22aX, 28-pentahydroxyolean-1 2 ene, named Ba9 R1 is O-acetyl, R2 is O-benzoyl, R3 is O-benzoyl 20 3-0-[ -D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1 ->3)- -D-glucuronopyranosyl 21 -O-[3,4-dibenzoyl-- P-D-xylopyranosyl]-22-O-acetyl- 3s, 15c, 21 P, 22ax, 28 pentahydroxyolean-12-ene, named Bal0 3-0-[s-D-galactopyranosyl(1->2)]-s- D-xylopyranosyl (1->3)-s-D-glucuronopyranosyl 21-0-[3-angeloyl, 4-benzoyl--s-D-xylopyranosyl]- 3s, 15a, 21 P, 22c, 28 25 pentahydroxyolean-1 2-ene, named Ball 3-0-[ -D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1->3)-s-D-glucuronopyranosyl 21-0-[3,4-diangeloyl--p-D-xylopyranosyl]- 3p, 15ax, 21$, 22aX, 28-pentahydroxyolean 12-ene, named Bal2 WO 2009/117196 PCT/US2009/034115 13 3-0-[j-D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1 -3)-p-D-glucuronopyranosyl 21-0-[3-angeloyl, 4-tigloyl--p-D-xylopyranosyl]- 3p, 15aX, 21 P, 22ca, 28 pentahydroxyolean-12-ene, named Ba13 3 29 25 26 OH 5 OH Wherein R1 is OH R2 is O-benzoyl, R3 is O-benzoyl 3-0-[j-D-galactopyranosyl(1->2)]- - D-xylopyranosyl (1 ->3)- -D-glucuronopyranosyl 21 -O-[3,4-dibenzoyl--ca-L-arabinopyranosyl]- 3p, 15x, 21 P, 22aX, 28-pentahydroxyolean 12-ene, named Bal4 10 Wherein R1 is O-acetyl, R2 is O-benzoyl, R3 is O-benzoyl 3-O-[p-D-galactopyranosyl(1->2)]-- D-xylopyranosyl (1 ->3)-p-D-glucuronopyranosyl 21 -0-[3,4-dibenzoyl--cx-L-arabinopyranosyl]-22-O-acetyl- 3p, 15a, 21 P, 22x, 28 pentahydroxyolean-12-ene, named Ba15 3~ 29 25 2. CH2OH C COOH 27 OH 0 00 C \O O 2H2 OH HOOH H HOH CH OH ,3-0-[P-D-galactopyranosyl(1 ->2)]-p- D-xylopyranosyl 15 (1 ->3)- P-D-glucuronopyranosyl-21 -O-[3-angeloyl-4-(3-benzoyl-2-methylbutyryl)-a-L arabinopyranosyl]-22-0-acetyl- 3p, 15a, 21 P, 22a, 28-pentahydroxyolean-1 2-ene, named Bal6

H

3 C 2 H29

H

3 C S 26 CHOH CH OH COOH 27 E HO OH H 0 2 H OH ;3-0-[j-D-galactopyranosyl(1 ->2)]-p- D xylopyranosyl (1->3)- -D-glucuronopyranosyl-21-0-angeloyl, 22-O-angeloyl-3, 15c, 20 16c, 21sP, 22a, 28-hexahydroxyolean-12-ene, also named Ba 17 WO 2009/117196 PCT/US2009/034115 14 Anti-cancer activities: The anti-cancer activity of Mb's compounds with ES2 cell: the IC50 of Mbl is 8ug/ml, Mb2 is /ml, Mb3 is 8ug/ml, Mb4 is 15ug/ml, Mb5 is 6.5ug/ml, and Mb6 is 10ug/ml, Mb7 is 12ug/ml, Mb8 is 20ug/ml, Mb9 is 18ug/ml, Mbl2 is 10ug/ml. 5 The anti-cancer activity of ACH's compounds with ES2 cell: the IC50 of ACH-Z4 is 40 ug/ml, ACH-Y3 is 20 ug/ml, ACH-Y1 0 is 20 ug/ml, ACH-Y2 is 35 ug/ml, ACH-Y8 is 35 ug/ml, ACH-Y7 is 65 ug/ml, ACH-YO is 20 ug/ml, ACH-X is 40ug/ml, ACH-E is 60 ug/ml The anti-cancer activity of Ba compounds with ES2 cell: Bal is 5 ug/ml, Ba2 is 5 ug/ml, 10 Ba3 is 8 ug/ml, Ba 5 is 16 ug/ml, Ba7 is 11 ug/ml, Ba8 is 20 ug/ml, Ba9 is 12 ug/ml, Bal7 is 5 ug/ml. The anti-cancer activity of Xanifolia Y with cells: the IC50 of Y on (bladder)TB9 cells is 5 ug/ml; IC50 of Y on (lung)H460 cells is 7.5 ug/ml; IC50 of Y on HeLa cells is 20 ug/ml; 15 IC50 of Y on skin cells is 12 ug/ml ; IC50 of Y on ES2(ovarian) cells is 5 ug/ml; IC50 of pure Y on (Mouth) KB cells is 6 ug/ml; IC50 of Z1 2 on ES2(ovarian) cells is 16 ug/ml; Z4 is 20ug/ml IC50 of Mb5: (bladder)TB9 is 6.5ug/ml, (Prostate) DU145 is 7.6 ug/ml, (Lung) H460 is 12 ug/ml (Liver) HepG2 is 6.5 ug/ml, (brain) T98G is 12 ug/ml, (Skin) SK-MELS is 25 20 ug/ml, (Ovary)ES2 is 6.5 ug/ml, (Breast)MCF7 is 11 ug/ml. IC 50 of ACH-Mb5: (bladder)TB9 is 5.7ug/ml, (Prostate) DU145 is 6.4 ug/ml, (Lung) H460 is 6.5 ug/ml (Liver) HepG2 is 4 ug/ml, (brain) T98G is 6 ug/ml, (Skin) SK-MELS is 22 ug/ml, (Ovary)ES2 is 8 ug/ml, (Breast)MCF7 is 13 ug/ml. 25 This invention provides a method and composition for reducing of adhesion protein to cure the diseases, wherein the diseases comprise inhibiting cancer growth, reducing leg swelling, symptoms of chronic venous insufficiency, peripheral edema, antilipemic, chronic venous disease, varicose vein disease, varicose syndrome, venous stasis, expectorant, peripheral vascular disorders, cerebro-organic convulsion, cerebral 30 circulation disorder, cerebral edema, psychoses, dysmenorrheal, hemorrhoids, episiotomies, peripheral edema formation or postoperative swelling; for reducing symptoms of leg pain; for treating pruritis, lower leg volume, for reducing symptoms of pain; thrombosis, thromophlebitis; for preventing gastric ulcers antispasmotic, comprising administering to a subject, in need thereof, an effective amount of the 35 composition of this invention.

WO 2009/117196 PCT/US2009/034115 15 In an embodiment, the method comprises interacting with adhesion protien, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. In an embodiment, this invention provides a method of 5 reducing the secretion of fibronectin. In an embodiment, the method comprises reducing the adhesion ability of adhesion protein; wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, 10 heparin, tenascin, CD 54, CAM, elastin and FAK. In an embodiment, the method comprises modulating the secretion of adhesion protien, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, 15 tenascin, CD 54, CAM, elastin and FAK. In an embodiment, the method comprises blocking the secretion of adhesion protien, wherein the adhesion protein comprising fibronectin. In an embodiment the method is administering contacting an effective amount of the compound selected from formulas in this application. 20 In an embodiment, this invention provides a method and composition for modulating adhesion or angiogenesis of cancer cells, antiparasitics or manufacturing an adjuvant composition. In an embodiment, this invention provides a method of antiprotozoal comprising treating leishmaniases, amoebiasis, trypanosomiasis, toxoplasmosis and malaria. 25 This invention provides a use of compound for manufacture of medicament, a method and composition for altering the characteristic of adhesion protein to cure diseases, wherein the characteristic comprising adhesion ability, wherein the method comprises reducing the secretion of fibronectin, wherein the diseases comprise inhibiting cancer 30 growth, reducing leg swelling, symptoms of chronic venous insufficiency, peripheral edema, antilipemic, chronic venous disease, varicose vein disease, varicose syndrome, venous stasis, expectorant, peripheral vascular disorders, cerebro-organic convulsion, cerebral circulation disorder, cerebral edema, psychoses, dysmenorrheal, hemorrhoids, episiotomies, peripheral edema formation or postoperative swelling; for reducing 35 symptoms of leg pain; for treating pruritis, lower leg volume, for reducing symptoms of pain; thrombosis, thromophlebitis; for preventing gastric ulcers antispasmotic, WO 2009/117196 PCT/US2009/034115 16 comprising administering to a subject, in need thereof, an effective amount of the composition of this invention; wherein the adhesion proteins comprise fibronectin, integrins family, Myosin , vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK In an 5 embodiment the method is administering contacting an effective amount in a subject with the compound selected from formulas in this application. A process and method for administration of the composition, wherein administration is by intravenous injection, intravenous drip, intraperitoneal injection or oral administration; 10 wherein administration is by intravenous drip: 0.05-0.2mg/kg compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCl solution, or by intravenous injection: 0.05-0.2mg/kg/day compound dissolved in 10-20ml of 10% glucose solution or of 0.9% NaCl solution, or by intravenous drip: 0.1-0.2mg/kg/day compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCl solution, or by intravenous 15 injection: 0.1-0.2mg/kg/day compound dissolved in 10-20ml of 10% glucose solution or of 0.9% NaCl solution, or by intraperitoneal injection(l.P.): 2.5mg/kg/day compound dissolved in 10% glucose solution or of 0.9% NaCl solution, or by oral administration wherein the dosage of mammal is 1-10mg/Kg, 10-30mg/Kg, 30-60mg/Kg, or 60 90mg/Kg compound, or by intravenous injection or intravenous drip wherein the dosage 20 of mammal is 0.01- 0.1mg/Kg, 0.1-0.2mg/Kg, 0.2 - 0.4mg/Kg, or 0.4 - 0.6 mg/Kg compound, or by intraperitoneal injection (l.P.) wherein the dosage of mammal is 1 3mg/Kg, 3-5mg/Kg, 4-6mg/Kg, or 6-1 0mg/Kg compound. The methods and uses of an isolated, purified or synthesized compound or its salt, ester, 25 metabolite or derivative thereof, having the formula of: R15 R14 R1 ---- 1R2 R11 R12 R R 13; R50 R R9 R1C also named (1A), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 alkyl, 0-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted 0 alkanoyl, 0-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, O-aryl, O-acyl, 30 0-heterocylic, 0-heteroraryl, and derivatives thereof; WO 2009/117196 PCT/US2009/034115 17 R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, O-heteroraryl, and derivatives thereof; 5 R4 represents CH 2 R6 or COR6, wherein R6 is selected from a group consisting of hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, O-di benzoyl, O-benzoyl, 0 alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; R3 is H or OH; R8 is H or OH; 10 R5 is a hydrogen, heterocyclic or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; wherein R9, R10, R11, R12, R13, R14, R15 are 15 independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO- heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0 heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, R2 and R6 are compriseing a group selected from O-angeloyl, O-tigloyl, 0 senecioyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted 20 O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, 25 aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; orwherein R4 is CH 2 R6; wherein R1 and R2 independently consists an O-angeloyl group, or at least two of R1, R2 and R6 are O-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two 0 angeloyls; or wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, 30 altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises glucuronic acid, arabinose and galactose. In an embodiment, wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, 35 galacturonic acid, and a derivative or combination thereof; in embodiment, the acyl has carbon 2 to 10.

WO 2009/117196 PCT/US2009/034115 18 In an embodiment the method is administering contacting the compounds, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound is having structure Xanifolia(Y), H HH OH O HO or chemical name: 3-0-[P-D-galactopyranosyl 5 (11 -2)]-a-L-arabinofuranosy (11 -3)- P-D-glucuronopyranosyl-21,22-O-diangeloyl-3 P, 15a, 16ax, 21 P, 22a, 28-hexahydroxyolean-12-ene; b) An isolated, purified or synthesized compound is having structure Xanifolia (Y1),

Y

1 < Ac H COOH OH H OH OH H OH or chemical name: 3-0-[p-D-galactopyranosyl (11 -2)] 10 a-L-arabinofuranosyl (1 ->3)-p-D-glucuronopyranosyl-21-O-(3,4-diangeloyl)-a-L rhamnophyranosyl-22-O-acetyl-3 ,16a, 21 , 22cx, 28-pentahydroxyolean-12-ene; c) An isolated, purified or synthesized compound is having structure Xanifolia (Y2),

Y

2 H, 0-C Y2 0 OH 0 OH 0 COGH 6 H OH H H H OHJ ZOHr OH or chemical name: 3-0-[p-D-glucopyranosyl 15 (1 -2)]-c-L-arabinofuranosy (11 -3)- P-D-glucuronopyranosyl-21,22-0-diangeloyl-3 P, 15a, 16ax, 21$, 22ax, 24$, 28-heptahydroxyolean-12-ene; d) An isolated, purified or synthesized compound is having structure Xanifolia (Y8), WO 2009/117196 PCT/US2009/034115 19 o--a 0" Y-8 N . 90 - OH 0 -"OH OHH OH0 H HO 0 HO OH or chemical name: 3-0-[,-glucopyranosyl (1->2)] a-arabinofuranosyl (1->3)-p-glucuronopyranosyl-21, 22-0-diangeloyl-3#, 16a, 21p6, 22a, 246, 28-hexahydroxyolean-12-ene; 5 e) An isolated, purified or synthesized compound is having structure Xanifolia (Y9), -0 Y9 "OH OAc "OH 0 OH OH \,C 0 OH HO 0 OH C-O O OH or chemical name:3-0-[#-galactopyranosyl (1->2)] a-arabinofuranosyl (1 ->3)-#-glucuronopyranosyl-21-O-(3,4-diangeloyl)-a rhamnopyranosyl-28-0-acetyl-3#3, 16a, 21, 22a, 28-pentahydroxyolean-12-ene; and 10 f) An isolated, purified or synthesized compound is having structure Xanifolia (Y1 0), Y-10 ' .0 OH 0 "OH OHO 0 HO OH or chemical name: 3-O-[#6-galactopyranosyl (1 ->2)]-a-arabinofuranosyl (1 ->3)-p-glucuronopyranosyl-21, 22-O-diangeloyl-3#8, 16a, 21#8, 22a, 28-pentahydroxyolean-12-ene. 15 g) An isolated, purified or synthesized compound is having structure Xanifolia (YO), H N -r CH 25 2 H OH HO OH HO O 00 H0 0 OH 0 H or chemical name: 3-0-[p-D galactopyranosyl(1 ->2)]-a-L-arabinofuranosyl(1 ->3)-p-D-glucuronopyranosyl-21 -0- WO 2009/117196 PCT/US2009/034115 20 angeloyl, 22-0-(2-methylpropanoyl)-3p, 15c, 16c, 21 , 22c, 28-hexahydroxyolean-12 ene, h) An isolated, purified or synthesized compound is having structure Xanifolia (X), H Ca 52 25 0 06 OH O~ 27 HO- O 24 *23 HO HO 0 HO ) 5 OH or chemical name: 3-O-{[p-D-galactopyranosyl (1 ->2)]-[ac-L-arabinofuranosy (1->3)]-p-D-glucuronopyranoside butyl ester}-21-0-acetyl 22-O-angeloyl- 36,16 a,21p6,22a,28-pentahydroxyolean-12-ene. i) An isolated, purified or synthesized compound is having structure (Y7), \ " H C - CH 0 OH H3C HD 23 0 C HO O HO 0H 0 20 0 10 OH or chemical name: 3-0-[-D-galactopyranosyl (1--2)]-a-L-arabinofuranosyl-(1--3)-f-D--glucuronopyranosyl-21-0-angeloyl-28-0-2 methylbutanoyl-3#, 15 a, 16a, 21#P, 22a, 28-hexahydroxyolean-12-ene j) An isolated, purified or synthesized compound is having structure (ACH): 0 - 3 29 - CH O25 0 OH 11 25 26 CHOH 27 O OH HO OH 15 (ACH-Y); 24 '23 ACH-Z4 30 29 C 30 29 CH 0 H

H

3 C H 3 C 25 26 CH 3 25 ""O CH 3 25 26 CH2 H 2 26 CH20 H 0 OH OH 27 272 HO HO OH 2 -23 ACH-Y10; HO 23 ACH-Y2; 30 292 30 "'29 O 0C"O H N~~~O 0 H 6 N '2 -, 25 26 CH2OH O 2 26 CH 7 OH OH O 27 27 HO HO OH H 3 ACH-Y8; 23 ACH-Y7; WO 2009/117196 PCT/US2009/034115 21 30 29 HC 30 29 H CC 0 CH CH, 0 HC 0 0 25 2. 0.. 99 --- 26 CH2OH 0 25 26 CH20H OH 'OH 27; 27 HO OH HO 2 23 ACH-YO; 23 OH ACH-E; 30 29 0 HC CH3C C OH 0 O -CH, 25 26 0 09C3 CHO 10 0 5 2HCOH CH3 H3C O - "~H 0 H 9 H0 HO O C, 27OH HO .

HO 2 23 ACH-X H3C 'H3 ACH-Mb5 OH 0 0 0 0 0 5 HO ACH-Mbl2 In an embodiment the method is administering contacting the compound, wherein the compound is selected from the following: k) An isolated, purified or synthesized compound is having a structure: Ha H, _ OHC H 21H C'~ mcH _ CH H22 H2 O ; O 27 3 H HO H O 10 ~ ~ O O0. 0 HO 10 OH IomounAn isolated, purified or synthesizedpud having a structure:lce ro olwn for mu la 26 2H2 0H 0 HO ~o 0 OH Y5 15 In an embodiment the method is administering contacting the compound, wherein the compound is isolated, purified or synthesized having a structure selected from following formulas: WO 2009/117196 PCT/US2009/034115 22 R1 R2 R4 (0 ), wherein R1, R2 are individually selected of an 0-acetyl or O-angeloyl; wherein the R3, R4, R5, R6, R7 is hydrogen or hydroxyl 5 In an embodiment the method is administering contacting the compound in this application comprising Xanifolia YO, Y1, Y2, Y, Y5, Y7, Y8, Y9, Y1 0, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof. In an embodiment the compound may be selected from formulas (1 A), (1 B), (1C), (1 D), (1 E), (1 F), (1 G), (1 H), (1 J), (1 K), (1 L). In an embodiment, the compound comprises a triterpene backbone, two angeloyl groups 10 and sugar moiety. In an embodiment the compound(s) are selected from Compound A to X and Al to X1 in the application. In an embodiment the compound(s) are selected from Compound Z1 to Z13 in the application. In an embodiment the method is administering contacting the compound comprise of a triterpene wherein the carbon position 21, 21 has an unsaturated group and sugar moieties at carbon 3. 15 In an embodiment, methods and compounds of this application reducing the adhesion ability inhibit bacteria in colonization and regulate tropism of cells. In an embodiment, reducing the adhesion ability of cell or viruses in order to inhibit 20 viruses binding to host cells, wherein the viruses comprise HIV. This invention provides a use of compound for manufacture of medicament, a method and composition for modulating adhesion or anti-angiogenesis of cancer tumor, antiparasitics or manufacturing an adjuvant composition, wherein the modulating 25 adhesion of cancer cell comprising modulating the secretion or expression of adhesion protein, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin , vitronectin, collagen, laminin, cadherin, heparin, tenascin, CD 54, CAM; wherein the modulating comprises reducing, inhibiting and stimulating, wherein modulating adhesion protein comprises reducing the fibronectin for inhibiting the metastasis or growth of 30 cancer cells, wherein the cancer is selected from breast cancer, leukocyte cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma WO 2009/117196 PCT/US2009/034115 23 cancer, and renal cancer; wherein the modulating adhesion of cancer cell comprising modulating the secretion or expression of adhesion protein, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin , vitronectin, collagen, laminin, cadherin, heparin, tenascin, CD 54, CAM; wherein the modulating comprises reducing, 5 inhibiting and stimulating; wherein the modulating angiogenesis comprises inhibiting and stimulating angiopoietin, wherein comprising angiopoietinl, angiopoietin 2, angiopoietin 3, angiopoietin 4, angiopoietin 5, angiopoietin 6 and angiopoietin 7; wherein the angiopoietin comprising angiopoietin-like 1, angiopoietin-like 2, angiopoietin -like 3, angiopoietin-like 4, angiopoietin-like 5, angiopoietin-like 6 and angiopoietin-like 7; 10 wherein the modulating comprises positive and negative regulating; wherein modulating angiopoietin comprises stimulating the angiopoietin 2 in order to inhibit angiogenesis; wherein modulating angiopoietin comprises inhibiting the angiopoietin 1 in order to inhibit angiogenesis; wherein modulating angiopoietin comprises inhibiting the angiopoietin-like 1; wherein modulating angiopoietin comprises inhibiting the 15 angiopoietin-like 4; wherein the antiparasitics comprise inhibiting leishmaniases, amoebiasis, trypanosomiasis, toxoplasmosis or malaria, wherein the method are is administering contacting the compound in this application comprising Xanifolia YO, Y1, Y2, Y, Y5, Y7, Y8, Y9, Y10, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof. In an embodiment the compound may be selected from formulas (1A), (1B), 20 (1C), (1 D), (1 E), (1 F), (1 G), (1 H), (1 J), (1 K), (1 L). In an embodiment, the compound comprises a triterpene backbone, two angeloyl groups and sugar moiety. In an embodiment the compound(s) are selected from Compound A to X and Al to X1 in the application. In an embodiment the compound(s) are selected from Compound Z1 to Z13 in the application. In an embodiment the compound(s) are selected from ACH-Z4, ACH 25 Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, ACH-Mb5 and ACHMb12. In an embodiment the saponins comprise Ba1, Ba2, Ba3, Ba4, Ba5, Ba6, Ba7, Ba8, Ba9, Bal0, Bal1, Bal2, Bal3, Bal4, Bal5, Bal6, and Bal7. In an embodiment the saponins comprise Mbl, Mb2, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, Mbl0, Mb11, Mbl2, and Mbl3. 30 In an embodiment, the methods and compositions of this application can be used for manufacturing an adjuvant vaccine, wherein the methods and compositions are used for manufacturing an adjuvant vaccine in a subject, wherein the method is administering contacting the compound in this application comprising Xanifolia YO, Y1, Y2, Y, Y5, Y7, 35 Y8, Y9, Y10, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof. In an embodiment the compound may be selected from formulas (1 A), (1 B), (1C), (1 D), (1 E), WO 2009/117196 PCT/US2009/034115 24 (1F), (1G), (1H), (1J), (1K), (1L). In an embodiment, the compound comprises a triterpene backbone, two angeloyl groups and sugar moiety. In an embodiment the compound(s) are selected from Compound A to X and Al to Xl in the application. In an embodiment the compound(s) are selected from Compound Z1 to Z1 3 in the application. 5 In an embodiment the compound(s) are selected from ACH-Z4, ACH-YlO, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, ACH-Mb5 and ACH-Mbl2. In an embodiment the saponins comprise Bal, Ba2, Ba3, Ba4, Ba5, Ba6, Ba7, Ba8, Ba9, Ba10, Ball, Ba12, Ba13, Ba14, Ba15, Ba16, and Ba 17. In an embodiment the saponins comprise Mbl, Mb2, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, MblO, Mbll, 10 Mbl2 and Mbl3. In an embodiment, this application provides an adjuvant composition comprising a saponin or compound selecting from above; wherein the composition is comprised of an immunostimulatory oligonuclcotide. In an embodiment, the methods and compositions of this application can be used for 15 manufacture of medicament for vaccine or antiviral agent for Enterovirus comprising EV71, wherein the method is administering contacting the cell or subject with compounds selected in this application comprising Mb1, Mb2, Mb3, Mb4, Mb5, Mb6, Mb7, Mb8, Mb9, Mb1 0, Mbl 1, Mbl 2 and Mb1 3. 20 The composition comprises the bioactive compounds from natural plants or synthesis. The majority of the plants are from the Sapindaceae family, which has 140-150 genera with 1400-2000 species. The program is based on our purification methods and biological assays including the MTT assay See International Application No. PCT/US05/31900, filed September 7, 2005, U.S. Serial No. 11/289142, filed November 25 28, 2005, and U.S. Serial No. 11/131551, filed May 17, 2005, and PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008, the contents of which are incorporated herein by reference. The details of Analysis of gene expression of ES2 cells after Y-treatment by Microarray, Data Analysis Methods and Western blot in PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008, the contents of which 30 are incorporated herein by reference This invention provides a composition comprising an effective amount of triterpenoidal saponins named as Xanifolia Y1, Y2, Y, Y5, Y7, Y8, Y9, Y10, and YO or their salt or their derivatives. In an embodiment the saponins comprise Bal, Ba2, Ba3, Ba4, Ba5, 35 Ba6, Ba7, Ba8, Ba9, Bal0, Bal1, Bal2, Bal3, Bal4, Bal5, Bal6, and Bal7 or their salt or their derivatives. In an embodiment the saponins comprise Mbl, Mb2, Mb3, Mb4, WO 2009/117196 PCT/US2009/034115 25 Mb5, Mb6, Mb7, Mb8, Mb9, Mbl0, Mbl1, Mbl2 and Mbl3, or their salt or their derivatives for modulating the adhesion protein, reducing adhesion protein or reducing the secretion of fibronectin, for treating chronic venous insufficiency, peripheral edema, antilipemic, chronic venous disease, varicose vein disease, varicose syndrome, venous 5 stasis, expectorant, peripheral vascular disorders, cerebro-organic convulsion, cerebral circulation disorder, cerebral edema, psychoses, dysmenorrheal, hemorrhoids, episiotomies, peripheral edema formation or postoperative swelling; for reducing symptoms of pain; for reducing symptoms of stomach pain; for reducing symptoms of leg pain; for treating pruritis, lower leg volume, thrombosis, thromophlebitis; for treating 10 rheumatism; for preventing gastric ulcers antispasmotic; blocking the migration, metastasis of cancer cells or inhibiting tumor growth. In an embodiment the method is administering contacting the compound in this application comprising Xanifolia YO, Y1, Y2, Y, Y5, Y7, Y8, Y9, Y10, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof. In an embodiment the compound may be selected from formulas (1A), (1B), 15 (1C), (1 D), (1 E), (1 F), (1 G), (1 H), (1 J), (1 K), (1 L). In an embodiment, the compound comprises a triterpene backbone, two angeloyl groups and sugar moiety. In an embodiment the compound(s) are selected from Compound A to X and Al to X1 in the application. In an embodiment the compound(s) are selected from Compound Z1 to Z13 in the application. In an embodiment the compound(s) are selected from ACH-Z4, ACH 20 Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, ACH-Mb5 and ACH-Mbl2. The compounds of this invention can be isolated from natural sources or synthesized. See experiments results in this application and see PCT/US05/31900, filed September 7, 2006; U.S. Serial No. 10/906,303, filed February 14, 2005; International Application 25 No. PCT/US04/43465, filed December 23, 2004; International Application No. PCT/US04/33359, filed October 8, 2004 and U.S. Serial No. 11/131551, filed May 17, 2005, PCT/US2007/077273, filed August 30, 2007, PCT/US2008/002086, 1188-ALA PCT, filed February 15, 2008, US61/038277 filed March 20, 2008, US61/054308, filed May 19, 2008, the contents of which are incorporated herein by reference. 30 Acid Hydrolysis of Saponin 15 mg Xanifolia-Y was dissolved in 1 ml of Methanol. 1 ml of 2N HCI was then added. The mixture was refluxed in 80C water bath for 5 hours. The solution was then neutralized by adding 2 ml of 1 N NaOH (to final pH 4-6). The aglycone was then 35 extracted with ethylacetate 3 ml x 2. The extracts were collected and pooled. Further isolation of aglycone (ACH-Y) was achieved by HPLC with isocratic elution of 80 -100% WO 2009/117196 PCT/US2009/034115 26 acetonitrile. Repeat the experiment with compound Z4, Y10, Y2, Y8, Y7, YO, X, and ESCIN were obtained compounds ACH-Z4, ACH-Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E, ACH-Mbl2, ACH-Mb5. 5 In mild conditions, the saponin will be partial hydrolysis to a mixture of products. The procucts can be separated by HPLC. Also, specific partial hydrolysis can be achieved with enzymes. The P-glucosidase is good enzyme to cleave of the P-glucose from saponin. 10 Removal of the acyl group by alkaline hydrolysis 20 mg of Xanifolia-Y was dissolved in 0.5 ml of 1 M NaOH. The solution was incubated in 80C water bath for 4 hours. It was cooled to room temperature before neutralized with 0.5 ml 1 N HCI (adjust pH to about 3). The mixture was extracted with 2 ml 1-butanol 3 times. The butanol fractions were collected and lyophilized. The hydrolyzed saponin 15 with further purified with HPLC in a C-18 column eluted with 25% acetonitrile. OH O CH O OHOH OH OH H OH Ho 0 OOH' o H H HO HO 0 OH OH AKOH-Y; H. OH AKOH-Mb5 Compounds AKOH-Y and AKOH-Mb5 have lost anticancer activity. 20 This invention provides a use of compound for manufacture of medicament or a method of modulating the adhesion proteins or their receptors, reducing the adhesion ability of the cancer cells, wherein the modulating comprises the positive or negative regulating. In an embodiment, the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, 25 heparin, tenascin, CD 54, CAM, elastin and FAK. In an embodiment, the method is reducing the secretion of fibronectin. This invention provides a method of blocking the migration, metastasis of cancer cells or inhibiting cancer cell growth or inhibiting leishmaniases modulating adhesion or inhibiting angiogenesis of cancer tumor, antiparasitics or manufacturing an adjuvant composition comprising 30 administering an effective amount of a pharmaceutical composition comprising a composition comprises the molecular formula or compound in this invention. The cancers comprise Leukemia cancer, Lung cancer, Colon cancer, CNS cancer, WO 2009/117196 PCT/US2009/034115 27 Melanoma cancer, ovarian cancer, renal cancer, Prostate cancer, Breast cancer, bladder cancer, cervix cancer, liver cancer, bone cancer, brain cancer and Skin cancer. The compounds of this invention can be isolated from natural sources or synthesized. In an embodiment the method is administering contacting the compounds, wherein the 5 compound is selected from the following: (Z1) 3-0-[P-D-galactopyranosyl(1 ->2)]-ax-L-arabinofuranosyl(1 ->3)P- D glucuronopyranosyl-21-0-angeloyl, 22-O-(2-methylpropanoyl)-3 , 15C, 16cr, 21 , 22a, 28-hexahydroxyolean-1 2-ene; 10 (Z2) 3-0-[#-D-galactopyranosyl-(1--2)]-a-L-arabinofuranosyl-(1--3)--D -glucuronopyranosyl-21 -0-angeloyl-22-0-(angeloyl-2-methylbutanoyl) -3#, 15 a, 16cr, 21/8, 22a, 28-hexahydroxyolean-12-ene; 15 (Z3) 3-0-[ P-D-galactopyranosyl(1 ->2)]-ar-L-arabinofuranosyl(1 ->3)-P-D glucuronopyranosyl-21-0-(2-methylpropanoyl), 22-0-(2-methylpropanoyl)-3p, 15cr, 16aX, 21p, 22cr, 28-hexahydroxyolean-12-ene; (Z4) 3-0-[s-D-galactopyranosyl(1 ->2)]-a-L-arabinofuranosyl(1 ->3)-P-D 20 glucuronopyranosyl-21 -0-angeloyl, 22-0-benzoyl-3p, 15cr, 16cr, 21 P, 22c, 28 hexahydroxyolean-1 2-ene; (Z5) 3-0-[ P-D-galactopyranosyl(1 ->2)]-a-L-arabinofuranosyl(1 ->3)- P-D glucuronopyranosyl-21 -0-angeloyl, 22-0-angeloyl-3p, 15a, 16cr, 21 P, 22cr, 28 25 hexahydroxyolean-1 2-ene; (Z6) 3-0-[-D-galactopyranosyl(1 ->2)]-cr-L-arabinofuranosyl(1 ->3)-3-D glucuronopyranosyl-21 -O-(2-methylpropanoyl)-O-benzoyl, 22-O-(2-methylpropanoyl) 3p, 15cr, 16cr, 21 P, 22cr, 28-hexahydroxyolean-12-ene; 30 (Z7) 3-0-[P-D-galactopyranosyl(1 ->2)]-ar-L-arabinofuranosyl(1 -43)-P-D glucuronopyranosyl-21-O-(2-methylpropanoyl)-O-angeloyl, 22-0-(2- methylbutanoyl) 3p, 15cr, 16cr, 21 P, 22cr, 28-hexahydroxyolean-12-ene; WO 2009/117196 PCT/US2009/0341 15 28 (Z8) 3-O-[J-D-galactopyranosyl(1 -42)]-c-L-arabinofuranosy(1 -43)-13-D glucuronopyranosyl-21 -O-benzoyl, 22-O-benzoyl-33, 1 5(x, 1 6c', 21 P3, 22cs, 28 hexahydroxyolean-] 2-ene; 5 (Z9) 3-O-[1-D-galactopyranosyl(1 --- 2)]-p3- D-xylopyranosyl (1 -*>3)-j3-D glucuronopyranosyl-21 -0-angeloyl, 22-O-benzoyl-3pj, 1 5cx, 1 6cX, 21 P3, 22cL, 28 hexahydroxyolean-1 2-ene; 33 N. 2 7 22H HOHH OH o OH Z1o 1 0 3-O-[j3-D-galactopyranosyl(1 ->2)]-3- D-xylopyranosyl -(1 ---3)-13-D-glucuronopyranosy 21 -0- (2- methyl propan oyl), 22-0- (2- methyl pro pan oyl)-3pj, 1 5cL, 1 6cX, 21 P, 22cL, 28 hexahydroxyolean-1 2-ene; 20 c 6H0 cCCHr o o, 2 7 OH OH, OH OH 7i1 1 5 3-O-[/3-D-galactopyranosyl-(1 -- *2)]- P3- D-xylopyranosyl -(1 -->3)-f3-D -glucuronopyranosyl-21 - O-angeloyl-22-0-(angeloyl-2-methylbutanoyl) -3p3, 15 a, 1 6a, 21P3, 22a, 28-hexahydroxyolean-1 2-ene; 05 . ~OHOH OH O 27o o, 0 OH HOH 71 2, 3-0-[13-D-galactopyranosyl(1 ->2)]-p3- D-xylopyranosyl (1 -*3)-1-D-glucuronopyranosyl 20 21-0-angeloyl, 22-0- tigloyl -313, 16c', 213, 22x, 28-pentahydroxyolean-12-ene; WO 2009/117196 PCT/US2009/034115 29 H CH HO CH HO OH Z13 3-0-[j-D-galactopyranosyl(1 ->2)]-a-L-arabinofuranosyl(1 ->3)-p-D-glucuronopyranosyl 21-0-angeloyl, 22-0- tigloyl -3s, 15a, 16a, 21sP, 22ax, 28-hexahydroxyolean-12-ene; 5 This invention provides uses of a compound for manufacture of medicament selected from formula (1 B), for modulating, regulating or interact with the adhesion protien, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. In an embodiment, this invention provides a 10 method of reducing the secretion of fibronectin, modulating adhesion or angiogenesis of cancer cells, antiparasitics, enhancing an immune response, providing adjuvant activities or providing vaccine activities, inhibiting cancer metastasis or growth,using the compounds selected for the following: 30 29

OR

1 "m'OR 2 25 26 . . R4 7R8 27 RO 23 24 R 3 ,also named as (1B), 15 or a salt, ester, metabolite or derivative thereof, wherein R1 comprises a group selected from hydrogen, angeloyl, acetyl, tigloyl, senecioyl, alkyl, dibenzoyl, benzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, acyl, aryl, heterocylic, heteroraryl, alkenylcarbonyl and derivatives thereof; R2 comprises a group selected from hydrogen, angeloyl, acetyl, tigloyl, senecioyl, alkyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl 20 alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl and derivative thereof; R4 represents CH 2 0R6 or COOR6, wherein R6 is selected from hydrogen, angeloyl, acetyl, tigloyl, senecioyl, alkyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl and derivative thereof; R3 is H or OH; wherein at least one of R1, R2,and R6 comprises a 25 group selected from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl and derivative thereof; R5 comprises a hydrogen or sugar moiety, wherein the sugar moiety comprises at least one sugar of, but is not limited to, D-glucose, D-galactose, L- WO 2009/117196 PCT/US2009/034115 30 rhamnose, L-arabinose, D-xylose, alduronic acid: D-glucuronic acid, D-galacturonic acid or a derivative thereof, or the combination thereof. In an embodiment, R1 comprises a sugar moiety wherein substituted with two groups 5 selecting from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic heteroraryl and a derivative thereof. In an embodiment, R1 comprises a sugar moiety wherein substituted with at least one group selecting from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl 10 and a derivative thereof. In an embodiment, R2 comprises a sugar moiety wherein at least one group is selected from angeloyl, acetyl, tigloyl, senecioyl, alkyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl and a derivative thereof. In an embodiment, R2 comprises a sugar moiety or a side chain wherein at least two groups are selected from angeloyl, acetyl, tigloyl, 15 senecioyl, alkyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl and a derivative thereof. In an embodiment, R4 comprises CH 2 OR6 or COOR6 wherein R6 is a sugar moiety which comprises at least one group selected from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl 20 and a derivative thereof. In an embodiment, R4 comprises CH 2 OR6 orCOOR6, wherein R6 is a sugar moiety which comprises at least two groups selected from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substitutedalkanoyl, aryl, acyl, heterocylic, heteroraryl and a derivative thereof. In an embodiment, R4 comprises CH 2 OR6 or COOR6, wherein R6 is a sugar moiety which 25 comprises at least two groups selected from angeloyl, acetyl, tigloyl and senecioyl. In an embodiment, R4 comprises CH 2 OR6 or COOR6 of formula (1 B), at least two of R1, R2 and R6 comprise the group selected from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl and a derivative thereof. In an embodiment, R4 comprises CH 2 OR6 or 30 COOR6 of formula (1B), wherein at least two of R1, R2 and R6 comprise angeloyl, benzoyl, alkenoyl, or a derivative thereof. In an embodiment, R4 is a side chain comprising CH 2 0COCH 3 , CH 2 COO-alkyl, CH 2 OH, COOH, angeloyl, acetyl, tigloyl, senecioyl, alkyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic or heteroraryl, alkanoyl substituted phenyl, alkenoyl 35 substituted phenyl, or a derivative thereof. In a further embodiment, R5 comprises a sugar moiety, wherein the sugar moiety comprises one or more sugar of, but is not WO 2009/117196 PCT/US2009/034115 31 limited to glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, or alduronic acid: glucuronic acid, galacturonic acid, or derivatives thereof, or the combination thereof. In an embodiment, R5 comprises a sugar moiety or a group 5 capable of performing the function of the sugar moiety. In an embodiment, the R5 represents H. In an embodiment, R4 represents H, OH or CH 3 . In an embodiment, position C23, C24, C25, C26, C29 and C30 of the compound independently comprise

CH

3 , CH 2 OH, CHO, COOH, COOa-Ikyl, COO-aryl, COO-heterocyclic, COO-heteroaryl,

CH

2 Oaryl, CH 2 0- heterocyclic, CH 2 O- heteroaryl, alkyls group, acetyl group or 10 derivatives thereof, particular CH3. In an embodiment, R1 and R2 independently comprise an angeloyl group. In an embodiment, R1 is a sugar moiety or a side chain which comprise two angeloyl groups. In an embodiment, R1 and R2 independently comprise a benzoyl group. In an embodiment, R1 is a sugar moiety which is substituted with two benzoly groups. In an embodiment, R 3 represents H or OH. In an embodiment, 15 R8 may be OH. In an embodiment, the 0 at C21, 22 may be replaced by N. In an embodiment, this invention provides a method of reducing the secretion of fibronectin; wherein the medicament is for inhibiting tumor or cancer cell growth and for treating cancer, wherein the cancers comprise breast cancer, leukocyte cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin cancer, bone cancer, brain cancer, 20 leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer or cervix cancer. Substitution, deletion and/or addition of any group in the above described compounds by other group(s) will be apparent to one of ordinary skill in the art based on the teachings of this application. In a further embodiment, the substitution, deletion and/or addition of the group(s) in the compound of the invention does not 25 substantially affect the biological function of the compound. This invention provides uses, methods, processes, compounds and compositions for modulating adhesion or angiogenesis of cancer cells, antiparasitics, enhancing an immune response, providing adjuvant activities or providing vaccine activities, inhibiting 30 cancer metastasis or growth, reducing adhesion protein of cells, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. In an embodiment, methods comprise inhibiting the gene expression. In an embodiment, this invention provides a method of reducing the 35 secretion of fibronectin. In an embodiment the method can block the migration, metastasis of cancer cells or inhibit the growth of cancers or anti-angiogenesis, wherein WO 2009/117196 PCT/US2009/034115 32 the cancers comprise breast cancer, leukocyte cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervix cancer, esophagus cancer, testis cancer, spleen cancer, kidney cancer, lymph cancer, 5 pancreas cancer, stomach cancer and thyroid cancer, In an embodiment the compounds are anti-angiogenesis, inhibiting cancer cell metastasis and inhibiting cancer growth, In an embodiment the compounds promote angiopoietin 2 . In an embodiment the compound is selected from the following formulas (1 E). In an embodiment the method is administering contacting the compounds, wherein the 10 compound is selected from the formula (1 E): R, ~R 1 4

R

1 6

R

4

R

11

R

12 RI, R13 'R R 0

R

3 R0 R 1 0 , also named (1 E), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 15 heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; 20 R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, 0 angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0-dibenzoyl, O-benzoyl, 0-alkanoyl, 0 alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, 0 alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, 0 alkenylcarbonyl and derivatives thereof; R3 is H or OH; R8 is H or OH, particularly OH; 25 R16 is H ,or R4 and R16 may together form -CH2-X-, CH(OH)-X- or C(=O)-X-, wherein the -X- may be 0 or N ; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R1 6 is absent. R5 is a hydrogen, heterocyclic or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, 30 xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; wherein R9, R10, R11, R12, R13, R14, R15 are WO 2009/117196 PCT/US2009/034115 33 independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO- heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0 heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein R4 and R16 form a divalent radical of formula CH20, CH(OR7)O, or COOR7, wherein R7 is 5 hydrogen, alkyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and derivatives thereof; wherein at least two of R1, R2 and R6 are compriseing a group selected from O-angeloyl, O-tigloyl, O-senecioyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, 0 benzoyl alkyl substituted O-alkanoyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, and 10 derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; or wherein R4 is CH 2 R6; wherein R1 and R2 independently consists an O-angeloyl group, or at least two of R1, R2 and 15 R6 are O-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two 0 angeloyls; wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the 20 combination thereof; wherein the sugar preferably comprises glucuronic acid, arabinose and galactose. In an embodiment, wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, galacturonic acid, and a derivative or combination thereof. In an embodiment, wherein R5 is 3- -O-{[(a-L-rhamnopyranosyl-(1 -*2)]-a-L-rhamnopyranosyl--(1 -*2)-p-D 25 galactopyranosyl--(1 ->3)]-[P-D- galactopyranosyl--(1 ->2)]- P-D-glucuronopyranosyl}. In an embodiment, wherein the carbon ring 3 comprises a double bond when R16 is H; wherein the double bond in carbon ring 3 is reduced when R4 and R16 form a divalent radical. 30 In an embodiment the method is administering contacting the compounds, wherein the compound is selected from the formula (1 F): WO 2009/117196 PCT/US2009/034115 34

R

4 R, 0

R

11

R

1 R4 R12 "R2 13 R

R

5 0 R 3 R, R 1 0 , also named (1 F), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, 0-senecioyl, O-alkyl, 0 dibenzoyl, 0-benzoyl, 0-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted 0-alkanoyl, 0-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, 0-aryl, 0-acyl, 0 5 heterocylic, O-heteroraryl, 0-alkenylcarbonyl and derivatives thereof; R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, 0-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, 0-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted 0-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, 0-aryl, O-acyl, 0 heterocylic, O-heteroraryl, 0-alkenylcarbonyl and derivatives thereof; 10 R4 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, 0-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, 0-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, 0-aryl, O-acyl, 0 heterocylic, O-heteroraryl, 0-alkenylcarbonyl and derivatives thereof; R3 is H or OH; R8 is H or OH, particularly OH; 15 R5 is a hydrogen or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; wherein R9, R10, R11, R12, R13, R14, R15 are independently 20 attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO-heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, R2 and R4 are compriseing a group selected from 0-angeloyl, O-tigloyl, O-senecioyl, 0 dibenzoyl, O-benzoyl, 0-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted 0-alkanoyl, 25 O-aryl, 0-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; or wherein R4, R1 and R2 independently consists an 0-angeloyl 30 group, or at least two of R1, R2 and R4 are O-angeloyl or at least one of R1, R2 or R4 is a sugar moiety with two O-angeloyls; wherein R5 is/are the sugar moiety(ies) WO 2009/117196 PCT/US2009/034115 35 selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises 5 glucuronic acid, arabinose and galactose. In an embodiment,wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, galacturonic acid, and a derivative or combination thereof; In an embodiment, wherein R5 is 3-p-O-{[(a-L-rhamnopyranosyl-(1 ->2)]-a-L rhamnopyranosyl--(1 -*2)-P-D- galactopyranosyl--(1 ->3)]-[P-D- galactopyranosyl- 10 (1 ->2)]- p-D-glucuronopyranosyl} In an embodiment the method is administering contacting the compounds of following: Ry Rl R R, OH Re R, R2 HO 0 O CH R12 R OH 00 R, R7 R, HO« 0 HOH HO 0 HO HO 0 H OH HO OH also named (1G), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 15 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, 20 0-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, 0 angeloyl, O-tigloyl, O-senecioyl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, 0 alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, 0 25 alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, 0 alkenylcarbonyl and derivatives thereof; R3 is H or OH; R5 is H or OH; wherein R6, R7, R8, R9, R1 0, R1 1, R1 2 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO-heterocyclic, COO heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0- heteroaryl, alkyls group, hydroxyl, 30 acetyl group, particularly CH 3

;

WO 2009/117196 PCT/US2009/034115 36 In an embodiment the method is administering contacting the compounds of following: R, 4~ R, 0 OH R, R 'R2 HO O 0 COOH R1: OH 00 R HOH 7 Re HO 00 HO R'eh OH HO 0 HO HO 00 H CH3 OH HO OH also named (1 H), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 5 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, 0-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, 0-heteroraryl, O-alkenylcarbonyl and derivatives thereof; R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, 10 O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; R4 is selected from hydroxyl, CH2OH, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 15 heterocylic, 0-heteroraryl, O-alkenylcarbonyl and derivatives thereof; R3 is H or OH; R5 is H or OH; wherein R6, R7, R8, R9, R10, R11, R12 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO- heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0 heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; 20 In an embodiment the use or method is administering contacting the compounds of following: R R, R, Rs R, R 0 0 R , HO R7 Re OH HO H l n H0 0 O H O H also named (1 J), wherein WO 2009/117196 PCT/US2009/034115 37 R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, 0-heteroraryl, O-alkenylcarbonyl and derivatives thereof; 5 R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0 dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0 heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, 0 10 angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0-dibenzoyl, O-benzoyl, 0-alkanoyl, 0 alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, 0 alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, 0 alkenylcarbonyl and derivatives thereof; R3 is H or OH; R5 is H or OH, particularly OH; wherein R6, R7, R8, R9, R10, R11, R12 15 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO alkyl, COO-aryl, COO-heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic,

CH

2 0- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; R13 is COOH or COO-alkyl, R1 OH HO 0 0 COOH R 4OH 00 R OHHRo HO O HO HO 0 H 1 OH 20 HO OH ; also named (1 L) wherein R1, R2 are angeloyl, R3 is OH, R4 is CH2OH, R5 is H or OH In an embodiment the method is administering contacting the compounds of following: H, 22 21 2 9 C CC2 H 0 COOH -1 = H HO OH HO02 OH Hr 0HO 0 OH OH or WO 2009/117196 PCT/US2009/034115 38 3-0-[j-D-galactopyranosyl(1->2)] -p- D-xyopyranosyl (1 -3)-p-D-glucuronopyranosyl 21 -0-angeloyl, 22-0-angeloyl-3B, 15x, 16cc, 21 P, 22ax, 28-hexahydroxyolean-1 2-ene, 3 29 HOO HD 0 24 >23 OH HO HO OH OH C OH OH ;or 5 3-0-[s-D-galactopyranosyl(1->2)]-s- D-xyopyranosyl (1 -3)-s-D-glucuronopyranosyl-21 O-benzoyl, 22-O-benzoyl-3p, 15(x, 16cc, 211P, 22(x, 28-hexahydroxyolean-1 2-ene o . 0 OHH OH ;or A sugar moiety is a segment of a molecule comprising one or more sugar groups. Substitution, deletion and/or addition of any group in the above-described compounds 15 will be apparent to one of ordinary skill in the art based on the teaching of this application. In a further embodiment, the substitution, deletion and/or addition of the group(s) in the compound of the invention does not substantially affect the biological function of the compound. 20 A method or a use of compound for manufacture of medicament of inhibiting venous insufficiency, particularly hemorrhoids or inhibiting leg swelling, or peripheral edema, antilipemic, chronic venous disease, varicose vein disease, varicose syndrome, venous stasis, Expectorant, peripheral vascular disorders, cerebro-organic convulsion, cerebral circulation disorder, cerebral edema, psychoses, dysmenorrheal, hemorrhoids, 25 episiotomies, hamonhoids, peripheral edema formation or postoperative swelling; for reducing symptoms of pain; for reducing symptoms of stomach pain; for reducing WO 2009/117196 PCT/US2009/034115 39 symptoms of leg pain; for treating pruritis, lower leg volume, thrombosis, thromophlebitis; for preventing gastric ulcers antispasmotic comprising administering to a subject, in need thereof, an effective amount of the composition of any one of the above compounds or a compound comprises a triterpene which comprises any two of 5 angeloyl, tigloyl, senecioyl, perferable two angeloyl groups, and a sugar moiety, glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid or galacturonic acid, or a derivative thereof, or the combination thereof, preferable selected from glucuronic acid, galacturonic acid, glucose, galactose and 10 arabinose. The method is regulating or interacting with adhesion protien, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK. In an embodiment, the method is reducing the secretion of fibronectin. In an embodiment, the method comprises inhibiting leishmaniases, 15 modulating adhesion or angiogenesis of cancer cells, antiparasitics or manufacturing an adjuvant composition. In an embodiment, antiparasitics comprise inhibiting leishmaniases, amoebiasis, trypanosomiasis, toxoplasmosis or malaria. This invention provides a method for inhibiting the growth, migration, metastasis of 20 cancer by altering the characteristic of membrane of cancer cell, wherein the characteristic comprise reducing adhesion protein; wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK; wherein comprising inhibiting the secretion of fibronectin, 25 wherein comprising administering to a subject, in need thereof, an appropriate amount of triterpenoidal saponins comprising two or more angeloyl groups, or a compound comprises a triterpene which comprises any two of angeloyl, tigloyl, senecioyl, perferable two angeloyl groups, and a sugar moiety, glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, 30 ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid or galacturonic acid, or a derivative thereof, or the combination thereof, preferably selected from glucuronic acid, galacturonic acid, glucose, galactose and arabinose. This invention provides a composition comprising an effective amount of the compound of any one of compound selected from the above formula or a salt, ester, metabolite or 35 derivative thereof as a medicament for reducing adhesion protein; wherein the adhesion proteins comprise fibronectin, integrins family, Myosin , vitronectin, collagen, laminin, WO 2009/117196 PCT/US2009/034115 40 Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK, for inhibiting the growth, migration, metastasis of cancer, wherein the cancers comprise breast cancer, leukocyte cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin cancer, bone cancer, brain cancer, 5 leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer or cervix cancer. This invention also provides a composition comprising the above described compounds or their derivatives for reducing adhesion protein, wherein the adhesion proteins 10 comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, Glycosylation cell surface proteins, polyglycans, cadherin, heparin, tenascin, CD 54, CAM, elastin and FAK; wherein comprising inhibiting the secretion of fibronectin, wherein for treating venous insufficiency, particularly hemorrhoids or inhibiting leg swelling, or peripheral edema, antilipemic, chronic venous disease, varicose vein 15 disease, varicose syndrome, venous stasis, Expectorant, peripheral vascular disorders, cerebro-organic convulsion, cerebral circulation disorder, cerebral edema, psychoses, dysmenorrheal, episiotomies, hemonhoids, peripheral edema formation or postoperative swelling; for reducing symptoms of pain; for reducing symptoms of stomach pain; for reducing symptoms of leg pain; for treating pruritis, lower leg volume, thrombosis, 20 thromophlebitis; for preventing gastric ulcers antispasmotic, inhibiting leishmaniases , for modulating adhesion or angiogenesis of cancer cells, antiparasitics or manufacturing an adjuvant composition. In an embodiment of the above, the uses of compositions comprising any one of triterpenoid saponins with the following formula: 3-0-{[p-D-galactopyranosyl (1 ->2)]-[a-L-arabinofuranosy (1 ->3)]-#8-D 25 glucuronopyranoside butyl ester}-21-O-acetyl-22-0-angeloyl-3, 16 a,21,,22a,28 pentahydroxyolean-1 2-ene. 3-0-[P-D-galactopyranosyl(1 ->2)]-a-L-arabinofuranosyl(1 ->3)-p-D-glucuronopyranosyl 21,22-O-diangeloyl-3p, 15a, 16ax, 21 P, 22a, 28-hexahydroxyolean-12-ene, 3-O-[p-D-galactopyranosyl(1 ->2)]-ax-L-arabinofuranosyl(1 -3)-p-D-glucuronopyranosyl 30 21-0-(3,4-diangeloyl)-ax-L-rhamnophyranosyl-22-0-acetyl-3 , 1 6aX, 21 P, 22ac, 28 pentahydroxyolean-1 2-ene, 3-0-[P-D-glucopyranosyl-(1 ->2)]-cc-L-arabinofuranosyl(1 ->3)-p-D-glucuronopyranosyl 21,22-O-diangeloyl-3p, 15a, 16cc, 21 P, 22a, 24P, 28-heptahydroxyolean-1 2-ene, 3-0-[p-glucopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-p-glucuronopyranosyl-21, 22 35 O-diangeloyl-3#, 16a, 21p6, 22a, 24p6, 28-hexahydroxyolean-12-ene, WO 2009/117196 PCT/US2009/034115 41 3-O-[#g-galactopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-,#-glucuronopyranosyl-21-0 (3,4-diangeloyl)-a-rhamnopyranosyl-28-0-acetyl-3#8, 16a, 21, 22a, 28 pentahydroxyolean-1 2-ene, 3-0-[p8-galactopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-#J-glucuronopyranosyl-21, 5 22-0-diangeloyl-3#8, 16a, 21P, 22a, 28-pentahydroxyolean-12-ene, 3-0-[j-D-galactopyranosyl(1->2)]-a-L-arabinofuranosyl(1->3)- -D-glucuronopyranosy I 21 -0-angeloyl, 22-0-(2-methylpropanoyl)-3p, 1 5cc, 16cx, 21 s, 22x, 28 hexahydroxyolean-1 2-ene, 3-0-[#-D-galactopyranosyl-(1 -- 2)]-a-L-arabinofuranosyl-(1 -->3)-p-D 10 -glucuronopyranosyl-21-0-angeloyl-28-0-2-methylbutanoyl-3#, 15 a, 16a, 21#8, 22a, 28 hexahydroxyolean-1 2-ene This invention also provides a composition for regulating or reducing adhesion protein, wherein the adhesion protein comprising fibronectin, integrins family, CD44, Myosin VI, 15 vitronectin collagen, laminin, Glycosylation cell surface proteins, polyglycans and FAK; inhibiting venous insufficiency, particularly hemorrhoids or inhibition of leg swelling, or inhibiting cancer growth, inhibiting leishmaniases, modulating adhesion of cancer cells, modulating angiogenesis of cancer cells, antiparasitics or manufacturing an adjuvant composition, comprising any of compounds selected from the following compounds (A) 20 to (X) and (Al) to (X1) incorporated here from PCT/US2008/002086, 1188-ALA-PCT,: In an embodiment, a triterpene comprise the following structure has activities of reducing adhesion proteins to blocks the migration, metastasis of cancer cells, growth of cancers, inhibiting leishmaniases, modulating adhesion or angiogenesis of cancer 25 cells, antiparasitics, or manufacturing an adjuvant composition. OR, "OR2 OR3 R5O.-"C(e) wherein at least two of R1, R2 and R3 comprise compounds selected from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, heterocylic, heteroraryl, alkanoyl substituted phenyl, alkenoyl 30 substituted phenyl, alkenylcarbonyl or substituted with an C2-9 acid or derivative thereof. In an embodiment, at least one of R1, R2 and R3 comprise a sugar moiety comprising two compounds selected from angeloyl, acetyl, tigloyl, senecioyl, alkyl, benzoyl, WO 2009/117196 PCT/US2009/034115 42 dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, alkenylcarbonyl or substituted with an C2-9 acid or derivative thereof. In embodiment, R1, R2 or R3 comprise angeloyl groups, tigloyl groups, senecioyl groups or acetyl group or their 5 combinations, preferable wherein at least two of the R1, R2 and R3 comprise angeloyl groups. In an embodiment, R5 comprises sugar moiety. In an embodiment, the sugar moiety comprises at least one sugar, or glucose, or galactose, or rhamnose, or arabinose, or xylose, or alduronic acid, or glucuronic acid, or galacturonic acid, or their derivative thereof, or the combination thereof. In an embodiment, the sugar moiety 10 comprises one or more sugar selected from, but is not limited to glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or the combination thereof. In an embodiment, the sugar moiety comprise glucose, galactose or arabinose, or combination thereof, or 15 derivatives thereof. In an embodiment, the sugar moietiy comprise alduronic acids, galactose and arabinose, wherein the alduronic comprise glucuronic acid or galacturonic acid. In an embodiment, the sugar moiety comprise alduronic acids, glucose and arabinose, wherein the alduronic comprise glucuronic acid or galacturonic acid. In an embodiment, R5 is Hydrogen. In an embodiment, the R1, R 2 and R3 may 20 be attached in other position of the structure. In an embodiment, the compound is triterpenoid saponin comprise comprises at least two angeloyl groups, tigloyl groups, senecioyl groups or acetyl group or their combinations, preferable wherein at least two angeloyl groups. 25 In an embodiment, at least two compounds selected from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, alkenylcarbonyl or substituted with an C2-9 acid or derivative thereof. 30 In an embodiment, at least one of the side bonds comprise a sugar moiety comprising two compounds selected from angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, alkenylcarbonyl or substituted 35 with an C2-9 acid or derivative thereof.

WO 2009/117196 PCT/US2009/034115 43 In an embodiment, the compound comprises a sugar moiety. In a further embodiment, the sugar moiety comprises glucose, galactose or arabinose or combination thereof. In a further embodiment, the sugar moiety comprises at least one sugar, or glucose, or 5 galactose, or rhamnose, or arabinose, or xylose, or alduronic acid, or glucuronic acid, or galacturonic acid, or their derivative thereof, or the combination thereof. In a further embodiment, the sugar moiety comprises one or more sugar selected from, but is not limited to glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, 10 altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or the combination thereof. A composition comprising an effective amount of compound selected from the above 15 formula or a salt, ester, metabolite or derivative thereof as a medicament for regulating or reducing adhesion protein, blocking the migration, metastasis of cancer cells, inhibiting tumor or cancer cell growth and for treating cancer, wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal and cervix cancer. 20 In a further embodiment, a compound or sapongenin comprises the structure (d) or (e) has anti-cancer or inhibiting virus activities. A composition for regulating or reducing adhesion protein, blocking the migration, 25 metastasis of cancer cells, treating cancers or inhibiting virus, comprising a compound, wherein the compound is a triterpene, which comprises at least two side chains which comprise angeloyl groups, wherein the side chains are at adjacent carbon in trans position. In an embodiment, the side chains are at alternate carbon in cis position. In an embodiment, the side chains are at alternate carbon in trans position. In an embodiment, 30 the side chains are attached an acyl. In an embodiment, the side chains are attached an unsaturated group. In an embodiment, the side chains are in non-adjacent carbon cis or trans position. In an embodiment, the side chains comprise a functional group capable of performing the 35 function of angeloyl group.

WO 2009/117196 PCT/US2009/034115 44 The above compounds can be used for regulating or reducing adhesion protein, blocking the migration, metastasis of cancer cells, inhibiting tumor cell growth, reducing leg swelling, symptoms of chronic venous insufficiency, peripheral edema, antilipemic, chronic venous disease, varicose vein disease, varicose syndrome, venous stasis, 5 expectorant, peripheral vascular disorders, by administering to a subject in need thereof, an effective amount of the above described compounds. This invention provides a method for inhibiting tumor cell growth, regulating cell growth, reducing inflammation, inhibiting leishmaniases, modulating adhesion or angiogenesis 10 of cancer cells, antiparasitics or manufacturing an adjuvant composition, comprising administering to a subject, in need thereof, an effective amount of the compound which comprises any of the above structures to said subject. The cancers are included but not limited to Leukemia cancer, Lung cancer, Colon cancer, CNS cancer, Melanoma cancer, Ovarian cancer, Renal cancer, Prostate cancer, Breast cancer, bladder cancer, cervix 15 cancer, liver cancer, bone cancer, brain cancer and Skin cancer. This invention also provides a method for reducing swelling, reducing symptoms of chronic venous insufficiency, peripheral edema, antilipemic, chronic venous disease, varicose vein disease, varicose syndrome, venous stasis, Expectorant, peripheral 20 vascular disorders, cerebro-organic convulsion, cerebral circulation disorder, cerebral edema, psychoses, dysmenorrheal, hemorrhoids, episiotomies, peripheral edema formation or postoperative swelling; for reducing symptoms of leg pain; for treating pruritis, lower leg volume, for reducing symptoms of pain; thrombosis, thromophlebitis; for preventing gastric ulcers antispasmotic, comprising administering to a subject, in 25 need thereof, an effective amount of the composition of this invention. This invention provides a composition comprising the compounds provided in the invention for treating cancers; for inhibiting virus; for preventing cerebral aging; for improving memory; improving cerebral functions, for curing enuresis, frequent 30 micturition, urinary incontinencedementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-Kappa B activation; for treating brain 35 edema, sever acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, anti-oedematous, anti inflammatory, WO 2009/117196 PCT/US2009/034115 45 hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling;for inhibiting blood clot, for inhibiting ethanol absorption; for lowering blood sugar; for regulating the adrenocorticotropin and corticosterone level. This invention provides a composition for AntiMS, antianeurysm, 5 antiasthmatic, antibradykinic, anticapillarihemorrhagic, anticephalagic, anticervicobrachialgic, antieclamptic, antiedemic, antiencaphalitic, antiepiglottitic, antiexudative, antiflu, antifracture, antigingivitic, antihematomic, antiherpetic, antihistaminic, antihydrathritic, antimeningitic, antioxidant, antiperiodontic, antiphlebitic, antipleuritic, antiraucedo, antirhinitic, antitonsilitic, antiulcer, antivaricose, antivertiginous, 10 cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cancer cells, antiparasitics, or manufacturing an adjuvant composition and venotonic treatment. 15 Alkenyl means unsaturated linear or branched structures and combinations thereof, having 1-7 carbon atoms, one or more double bonds therein. Non-limiting examples of alkenyl groups include vinyl, propenyl, isopropenyl, butenyl, s- and t-butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, and hexadienyl. 20 An aryl is a functional group of organic molecule derived from an aromatic compound such as benzene, a 6-14 membered carbocyclic aromatic ring system cpmprising 1-3 benzene rings. If two or more aromatic rings are present, then the rings are fused together, so that adjacent rings share a common bond. Examples include phenyl and naphthyl. The aryl group may be substituted with one or more sunstitutes independnetly 25 selected from halogen, alkyl or alkoxy. Acyl is a functional group obtained from an organic acid by the removal of the carboxyl. Acyl groups can be written as having the general formula -COR, where there is a double bond between the carbon and oxygen. The names of acyl groups typically end in -yl, 30 such as formyl, acetyl, propionyl, butyryl and benzoyl. Benzoyl is one of acyls, C 6

H

5 COR, obtained from benzoic acid by the removal of the carboxyl. Heterocyclic compound - a compound containing a heterocyclic ring which refers to a 35 non-aromatic ring having 1-4 heteroatoms said ring being isolated or fused to a second ring selected from 3- to 7-membered alicyclic ring containing 0-4 heteroatoms, aryl and WO 2009/117196 PCT/US2009/034115 46 heteroaryl , wherein said heterocyclic comprises pyrrolidinyl , pipyrazinyl morpholinyl, trahydrofuranyl, imidazolinyl, thiomorpholinyl, and the like. Heterocyclyl groups derived from heteroarenes by removal of a hydrogen atom from any ring atom. 5 Alkanoyl is the general name for an organic functional group RCO-, where R represents hydrogen or an alkyl group. Preferably alkanoyl is selected from acetyl, propionoyl, butyryl, isobutyryl, pentanoyl and hexanoyl. 10 Alkenoyl is alkenylcarbonyl in which alkenyl is defined above. Examples are pentenoyl(tigloyl) and hexenoyl(angeloyl). Alkyl is a radical containing only carbon and hydrogen atoms arranged in a chain, branched, cyclic or bicyclic structure or their combinations, having 1-18 carbon atoms. 15 Examples include but are not limited to methyl, ethyl, propyl isopropyl, butyl, s- and t butyl, pentyl, hexyl, heptyl, octyl, nonyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Benzoyl alkyl substituted alkanoyl is refer to straight or branched Cl-C6 alkanoyl 20 substituted with at least one benzoyl and at least one alkyl, wherein the benzoyl is attached to a straight or branched C1-C6 alkyl. Preferably a benzoyl alkyl substituted alkanoyl is benzoyl methyl isobutanoyl. A sugar moiety is a segment of molecule comprising one or more sugars or derivatives 25 thereof or alduronic acid thereof. Isobutyryl is Synonym of 2-Methylpropanoyl Y and Y3 represent the same compound. YM and (ACH-Y) represent the same compound. 30 WO 2009/117196 PCT/US2009/034115 47 (Z)-O(C=O)C(CH3)=CH-C6H5 is [0- -o C5 alkenoyl substituted with phenyl]

H

3 C (Z)-O(C=0)CH=CH-C6H5 is [0-C4 alkenoyl substituted with phenyl] -- il"- 0 (E)-O(C=O)CH=CH-C6H5 is [0-C4 alkenoyl substituted with phenyl] -o 0 O(C=0)C6H5, Benzoyl is [O-C2 alkanoyl substituted with phenyl] o O (2Z)-2-methyl-3-phenylacrylic acid HO H _C (2Z)-3-phenylacrylic acid HOA ___ 0 (2E)-3-phenylacrylic acid HO 0 Benzoic acid HO/

H

3 C O-Angeloyl: -0-C

CH

3 O(C=0)C(CH3)=CH(CH3) 0 WO 2009/117196 PCT/US2009/034115 48 This invention provides a method of altering the characteristic of cancer cell membrane to block the migration, metastasis of cancer cells or inhibit the growth of cancers or anti angiogenesis. 5 This invention provides a composition and method for inhibiting the growth, migration, metastasis of cancer by altering the adhesion characteristic of membrane of cancer cell, wherein the cancers comprise breast cancer, leukocyte cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal 10 cancer or cervix cancer, wherein the method is administering contacting Xanifolia YO, Y1, Y2, Y, Y5, Y7, Y8, Y9, Y10, or a salt, ester, metabolite thereof. In an embodiment the method is administering contacting the compound selected from formula in this application. 15 This application shows Xanifolia-Y is an alternate or supplemental agent to DNA inhibition or microtubule-targeting drugs. It could be beneficial if it is used singly or in combination with other drugs of different mechanisms (block M-phase progression or DNA synthesis). Our inventions show combined effect of Xanifolia-Y and paclitaxel on inhibition of ES2 cells' growth (Detail in Experiment 14 U.S. Serial Nos.11/683198, filed 20 on March 7, 2007) . Identify the binding target of Xanifolia-Y of adhesion proteins and signaling proteins in ovarian cancer cells. 25 In our animal studies, it was shown that Xanifolia-Y extended the life span of tumor bearing mice. (Reference Experiments 7, 8, 9 in U.S. Serial Nos.11/683198, filed on March 7, 2007,). The animals died sooner if the treatment of Xanifolia-Y was delayed (comparing results of treatments started from 1, 4 or 10 days after tumor inoculation). The results show that Xanifolia-Y inhibits migration or metastasis of the inoculated 30 cancer cells. Ovarian carcinoma cells express high levels of adhesion molecules. Adhesion proteins are present in both cancer cells and mesothelial cells. While the lost of adhesion blocks of the protein accessibility due to a result of modulating by Xanifolia Y, In an embodiment, the interaction of Xanifolia-Y with membrane alter the adhesion protein's binding site(s). 35 WO 2009/117196 PCT/US2009/034115 49 Fibronectin is a kind of glycoprotein that binds to membrane spanning receptor proteins comprising the integrins, collagen, fibrin and heparin sulfate. Fibronectin has been implicated in tumor development and metastasis. This application provides methods and compositions for modulating the gene expression of fibronectin, inhibiting the 5 secretion of fibronectin, reducing the receptors of fibronectin, reducing the adhesion ability fibronectin, inhibiting the metastasis, or inhibiting cancer growth, wherein the method and composition comprises administering to the said subject as effective amount of compounds selected in this appliaction. 10 Angiogenesis is a process involving the growth of new blood vessels. It is a normal process in growth and development. However, this is also a fundamental step in the transition of tumors from a dormant state to a malignant state. The angiopoietins are protein growth factors that modulate angiogenesis. The identified angiopoietins comprise angiopoietin 1, angiopoietin 2, angiopoietin 3, angiopoietin 4, angiopoietin 5, 15 angiopoietin 6, angiopoietin 7, angiopoietin-like 1, angiopoietin-like 2, angiopoietin-like 3, angiopoietin-like 4, angiopoietin-like 5, angiopoietin-like 6, and angiopoietin-like 7. In an embodiment, the angiopoietin 1 is a positive foctor to promote the new blood vessels. In embodiment, the angiopoietin 2 is antagonist of angiopoietin 1, which is a negative factor for the growth of new blood vessels. This application provides methods and 20 compositions for modulating angiopoietin and inhibiting cancer growth; wherein the cancers comprise breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal and cervix cancer, wherein the methods and compositions comprise administering to the said subject as effective amount of compounds selected in this appliaction. The compounds in this application are positive 25 regulating angiopoietin 2. The compounds in this application are negative regulating the angiopoietin 1. The results of the micro array experiment showed that compound Y and YM (ACH-Y) modulate the gene expression of angiopoietin family in ES2 cells. They promote angiopoietin 2 and inhibit angiopoietin 1 and angiopoietin-like 1 and angiopoietin-like 4. 30 The compounds in this application are used antiparasitics, enhancing an immune response, providing adjuvant activities or providing vaccine activities, anti-angiogenesis, inhibiting cancer cell metastasis and inhibiting cancer growth, wherein the compounds comprise Xanifolia YO, Y1, Y2, Y, Y7, Y8, Y9, Y10, ACH-Y or a salt, ester, metabolite 35 thereof and compounds selected from formula (1A), (1 B), (1C) , (1 D), (1 E), (1 F), (1 G), (1H), (1J), (1K), (1L). In an embodiment the method is administering contacting the WO 2009/117196 PCT/US2009/034115 50 compound in this application comprising Xanifolia YO, Y1, Y2, Y, Y7, Y8, Y9, Y10, Xanifolia (x), Escin or Aescin or a salt, ester, metabolite thereof. In an embodiment the compound may be selected from formulas (1 A), (1 B), (1 C), (1 D) (1 E), (1 F), (1 G), (1 H), (1 J), (1 K), (1 L). In an embodiment, the compound comprises a triterpene backbone, two 5 angeloyl groups and sugar moiety. In an embodiment the compound(s) are selected from Compound A to X and Al to X1 in the application. In an embodiment the compound(s) are selected from Compound Z1 to Z7 in the application. In an embodiment the compound(s) are selected from ACH-Z4, ACH-Y1 0, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-E. In an embodiment the saponins comprise Bal, Ba2, 10 Ba3, Ba4, Ba5, Ba6, Ba7, Ba8, Ba9, Bal0, Ball1, Bal2, Bal3, Bal4, Bal5, Bal6, Ba 17. The triterpene compounds of this invention can be administered to a subject in need thereof treating the subject, wherein including preventing canceror has adjuvant effect 15 to the subject, or inhibiting the initation or promotion of cancer, or killing the cancer/tumor cells. In an embodiment the compounds inhibit the activation of nuclear factor-kB, wherein inhibiting the localization or wherein binding the DNA. In an embodiment the compounds induce apoptosis in cancer cells. The triterpene compounds of this invention can reduce blood vessel in the tumor in a 20 subject. (Figure 1) Table 1 to 12, Effect of Y and YM on gene expression (Table of 1 to 12 PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008 are incorporated herein by reference) 25 Table 13: Effects of Y and YM on Glypican expression in ES2 cells Probe Set ID Y/D Ym/D Gene.Symbol Gene.Title 243865_x_at -2.7 -2.0 GPC6 Glypican 6 227059_at -2.2 -1.8 GPC6 Glypican 6 The results of the micro array experiment showed that compound Y and Ym inhibit gene expression of Glypican in ES2 cells. 30 Table 14: Effects of Y and YM on regulator of G-protein expression in ES2 cells Probe Set ID Y/D Ym/D Gene.Symbol Gene.Title 204339 s at -3.5 -1.2 RGS4 regulator of G-protein signalling 4 204337 at -3.4 -1.1 RGS4 regulator of G-protein signalling 4 204338 s at -2.5 -1.1 RGS4 regulator of G-protein signalling 4 WO 2009/117196 PCT/US2009/034115 51 The results of the micro array experiment showed that compound Y and YM inhibit gene expression of G-protein in ES2 cells Table 15: Effects of Y and YM on thrombospondin in ES2 cells Probe Set ID Y/D Ym/D Gene.Symbol Gene.Title 201109 s at -2.0 -6.2 THBS1 thrombospondin 1 201110 s at -1.8 -4.5 THBS1 thrombospondin 1 201108 s at -1.7 -2.2 THBS1 thrombospondin 1 5 The results of the micro array experiment showed that compound Y and YM inhibit gene expression of thrombospondin in ES2 cells Table 16: Effects of Y and YM on insulin-like growth factor binding protein expression in ES2 cells Probe Set ID Y/D YM/D Gene.Symbol Gene.Title insulin-like growth factor binding protein 210095 s at -4.0 -3.5 IGFBP3 3 insulin-like growth factor binding protein 212143 s at -3.7 -5.3 IGFBP3 3 insulin-like growth factor binding protein 201508 at -1.7 -2.4 IGFBP4 4 insulin-like growth factor binding protein 205302_at -1.7 -1.8 IGFBP1 1 insulin-like growth factor binding protein 201163 s at -1.4 -2.7 IGFBP7 7 insulin-like growth factor binding protein 203851 at -1.3 -1.8 IGFBP6 6 10 The results of the micro array experiment showed that compound Y and YM inhibit gene expression of insulin-like growth factor binding protein in ES2 cells. Table 17: Effects of Y and YM on RAB3B, member RAS oncogene family protein expression in ES2 cells ID Y/D YM/D Gene.Symbol Gene.Title 242629 at -3.5 -1.8 RAB3B RAB3B, member RAS oncogene family 205924 at -1.7 -1.8 RAB3B RAB3B, member RAS oncogene family 227123 at -1.6 -1.2 RAB3B RAB3B, member RAS oncogene family 205925 s at -1.2 -1.2 RAB3B RAB3B, member RAS oncogene family 15 The results of the micro array experiment showed that compound Y and Ym inhibit gene expression of RAB3B, member RAS oncogene family protein in ES2 cells.

WO 2009/117196 PCT/US2009/034115 52 Table 18: Effects of Y and YM on potassium channel, subfamily U, protein expression in ES2 cells ID Y/D YM/D Gene.Symbol Gene.Title potassium channel, 237273 at -4.0 -1.9 KCNU1 subfamily U, member 1 The results of the micro array experiment showed that compound Y and Ym inhibit gene expression of family protein relate to potassium channel in ES2 cells. 5 protein phosphatase 1, regulatory 37028_at 2.4 5.6 PPP1R15A (inhibitor) subunit 15A protein phosphatase 1, regulatory 202014_at 2.6 6.2 PPP1R15A (inhibitor) subunit 15A 215501 s at 3.2 7.1 DUSP10 dual specificity phosphatase 10 221563_at 3.8 5.7 DUSP10 dual specificity phosphatase 10 Fibronectin secretion studies summary: Reduction of Fibronectin secretion from ES2 cells after xanifolia-Y treatment. 10 (Results of F1, F3, F4, F5, F7, F8, F11, F12A, F15, F16, F17) Data in PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008 are incorporated herein by reference (Fl 1) For lung carcinoma cells (H460), at concentration of 20ug/ml, there are inhibitions of Fibronectin secretion ranged from 20-60%. 15 (F12A) For bladder carcinoma cells (HTB-9), Xanifolia-Y (10 ug/ml) inhibits 50% of Fibronectin secretion. (F1 5) In liver HepG2 cells. 10 ug/ml of xanifolia-Y inhibits 42% secretion of Fibronectin. (F16) Incubation of brain glioblastoma T98G cells with1Oug/ml of xanifolia-Y inhibits 20 27% Fibronectin secretion and with 20ug/ml Y inhibits74% Fibronectin secretion. (F1 7) For skin SK-Mel-5 cells, the inhibition is 40-57% with 20 ug/ml of Xanifolia-Y. Studies of xanifolia-Y analogs and other saponin on Fibronectin secretion from ES2 cells. Results of (F 23, F21, F 13, F14, F24, F25, 26, 31B, F27,29, F28, 30, F 31, 25 32, F 33, F20) in PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008) WO 2009/117196 PCT/US2009/034115 53 ES2 cells p-ES- X-10 YO-10 Y1-10 Y3-10 Y7-10 ACH-Y- AKOH-80 10 20 %inhibition 19 39 34 41 47 34 48 No effect Studies of other saponins on Fibronectin secretion from ES2 and other cells ES2 cells Mb12-10 Mb5-10 ACH-Mb5-10 Bal-10 Ba4-10 AKOH-Mb-40 %inhibition 30 35 30 30 28 No effect Liver HepG2 Mbl2-10 Mb5-10 ACH-Mb5-10 Bal-10 Ba4-10 %inhibition 30 35 25 33 28 5 Lung H460 Mb12-10 Mb5-10 ACH-Mb5-10 Bal-10 Ba4-10 %inhibition 20 25 22 19 18 Bladder HTB-9 Mb12-10 Mb5-10 ACH-Mb5-10 Bal-10 Ba4-10 % inhibition 32 28 30 25 30 10 Brain T98G Mb12-10 Mb5-10 ACH-Mb5-10 Bal-10 Ba4-10 % inhibition 40 33 35 26 24 Skin SK-MEL-5 Mb12-10 Mb5-10 ACH-Mb5-10 Bal-10 Ba4-10 % inhibition 17 15 20 10 10 15 Up regulation of Angiopoietin 2 (Ang2) in ES2 cells with Xanifolia-Y treatment. The results of study in PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008 are incorporated herein by reference. Data obtained from our Microarray experiments disclose that Xanifolia Y modulates 20 gene expression of the following genes (represented by gene symbol): Gene Symbol: ABL2, ADAMTS1, AKR1C3, AMIGO2, ANGPT2, ANKRD11, AP2B1, APEH, APLP2, AR10C, ARMC4, ARMCX1, ARMCX6, ARNTL2, ARNTL2, ATF3, ATP6VOE, ATP6V1 B2, ATP6V1 C1, ATP6V1 C1, BCL2A1, BCL6, BR13, BTD, 25 C14orf109, C14orf78, C17orf32, C6orf65,C9orf10, C9orf103, CAD, CAV1, CAV2, WO 2009/117196 PCT/US2009/034115 54 CBLL1, CCL20, CD33L3, CEBPB, CEP4, CFH // CFHL1, CHRDL1, CITED2, CITED2, CLDN14, CLN8, CLTA, CNAP1, COG6, COL18A1, COL4A2, COL5A1, COL5A2, COL6A3, COPG, CPM, CPNE3, CPSF1, CSRP2BP, CSTB, CTNS, CXCL2, DDB1, DDIT3, DDX20, DKFZP564I1171, DKFZP586JO619, DUSP10, DUSP10, DYRK3, 5 EEF2K, EFEMP1, EMP1, EVC, EVI2A, EXT2, FAM62A, FER1L3, FLJ14466, FLNA, FN1, FN1, GANAB, GDF15, GEM, GNPDA1, GPAA1, GPC6, GPNMB, GPNMB, GUSB, H2AFV, H2AFV, HDAC9, HDLBP, HECW2, HMGA2, HMOX1, HSDL2, HSPBAP1, HSPC196, HYOU1, IDS, IGFBP3, IKBKAP, INSIG1, IPO4, IRS2, JAG1, KDELR3, KIAA0251, KIAA0586, KIAA1211, KIAA1462, KIAA1706, KIAA1754, KRT18, KRT7, 10 KRTAP4-7, LAMP2, LEPR, LEPREL1, LHFPL2, LIF, LOC286044, LOC339229, LOC90693, LRRC8E, MAFG, MAGED2, MCTP1, MGC16291, MGC19764, MGC5618, MRPS30, MRPS31, MTERFD3, MYH9, NAGA, NAV2, NCSTN, NEK9, NEU1, NFKBIZ, NMT2, NPC2, NSUN5C, NTNG1, NUP188, OACT2, OS9, P4HA1, P8, PALM2-AKAP2, PALM2-AKAP2, PARVA, PBX2, PDE4DIP, PDIA4, PDIA6, PEG10, PHF19, PIK4CA, 15 PLEKHM1, PLOD1, PLOD2, PPP1R15A, PPP1R15A, PRKDC, PRSS23, PRSS23, PSEN2, PSMD1, PTPRF, PTPRJ, RAB32, RAB9A, RG9MTD1, RGS4, RHOQ, RND3, RNF25, RNPEP // UBE2V1 /// Kua /// Kua-UEV, RNU17D, ROBO4, RRAGC, RRS1, SEC31L1, SERPINB2, SERPINB7, SESN2, SGEF, SGSH, SKIV2L, SLC25A21, SLC35A3, SLC3A2, SMARCA1, SNAPC1, SNF1LK, SPOCD1, SPTAN1, SQSTM1, 20 ST3GAL6, STC2, STX3A, TFPI2, TFP12, TGFBI, TGM2, THRAP1, TLN1, TMEM60, TNFAIP3, TRIB3, TRIO, TSC2, UAP1L1, UBAP2L, UPP1, URB, USP11, USP5, VDR, WDR4, YTHDF2, ZCCHC9, ZDHHC20, ZFHX1B, ZNF1 85, ZNF278, ZNF690, ZNF697 Data obtained from our Microarray experiments disclose that Xanifolia Y inhibiting gene 25 expression of the following genes (represented by gene symbol): AKR1C3, SLC35A3, NEK9, CAV1, USP11, KRT7, TGM2, NCSTN, COG6, WDR4, GPAA1, GUSB, UBAP2L, NMT2, C9orf10, KIAA0251, BTD, EMP1, KRT18, OS9, CPSF1, PSMD1, RNPEP///UBE2V1 /// Kua /// Kua-UEV, NAGA, PARVA, HYOU1, ARMC4, APEH, BTD, FER1 L3, CFH /// CFHL1, COL5A2, EFEMP1, COL1 8A1, HSDL2, 30 NUP188, IDS, PLOD1, CPM, SPTAN1, LAMP2, ARNTL2, PLOD2, KDELR3, KIAA0586, SMARCA1, PRSS23, PTPRJ, LEPREL1, H2AFV, CAD, URB, CPNE3, DKFZP586JO619, SERPINB7, CNAP1, EEF2K, IKBKAP, SLC25A21, KDELR3, PDIA6, CAV2, COL4A2, MAGED2, PHF19, OACT2, JAG1, FAM62A, KDELR3, PIK4CA, USP5, ZDHHC20, H2AFV, PTPRF, PEG10, P4HA1, MAGED2, PRSS23, PTPRF, CHRDL1, 35 C6orf65, APLP2, EXT2, COPG, SKIV2L, PDIA4, MYH9, SEC311L1, GANAB, COL5A1, WO 2009/117196 PCT/US2009/034115 55 ZNF185, DDB1, HDLBP, AP2B1, TSC2, IPO4, FLNA, TLN1, PRKDC, COL6A3, NTNG1, LEPR, RGS4, FN1, GPC6, LEPR, RGS4,IGFBP3 Data obtained from our Microarray experiments disclose that Xanifolia Y stimulates 5 gene expression of the following genes (represented by gene symbol): P8, KRTAP4-7, DUSP10, CLDN14, ANGPT2, DUSP10, GDF15, GPNMB, HDAC9, HECW2, C14orf78, UPP1, PPP1R15A, PLEKHM1, STX3A, ANGPT2, SQSTM1, RHOQ, STC2, PPP1 R1 5A, LOC286044, ATF3, HMOX1, CXCL2, CD33L3, LRRC8E, SESN2, LIF, TFPI2, KIAA1706, RRAGC, DDIT3, DYRK3, CTNS, GPNMB, CEBPB, 10 CCL20, AMIGO2, KIAA1462, HSPBAP1, EVC, CLN8, ABL2, SGEF, MCTP1, IRS2, C14orf109, TNFAIP3, RND3, ZFHX1B, LHFPL2, SNF1LK, SLC3A2, NAV2, SPOCD1, TFP12, EV12A, ST3GAL6, CSTB, ROBO4, GNPDA1, GEM, IRS2, HMGA2, PALM2 AKAP2, BRI3, KIAA1754, VDR, NEU1, INSIGI, C17orf32, ABL2, PALM2-AKAP2, MTERFD3, ZNF697, NFKBIZ, BCL6, THRAP1, MGC5618, ADAMTS1, MAFG, NPC2, 15 CITED2, TRIB3, ZCCHC9, RNU17D, CITED2, RRS1, NSUN5C, PBX2, RG9MTD1, SGSH, INSIGI, MGC16291, RAB9A, ARMCX6, SERPINB2, ATP6V1B2, DKFZP56411171, ATP6VOE, HSPC196, MRPS30, ARMCX1, LOC339229, ANKRD11, C9orfl03, PSEN2, ADAMTS1, SNAPC1, RNF25, ZNF278, TGFBI, UAP1L1, PDE4DIP, MGC19764, TMEM60, CEP4, KIAA1211, DDX20, CSRP2BP, ZNF690, TRIO, CLTA, 20 ATP6VOE, RAB32, MRPS31, LOC90693, ATP6V1C1, CBLL1, YTHDF2, FLJ14466, ARL10C, BCL2A1 Data obtained from our Microarray experiments disclose that Xanifolia YM(ACH-Y) stimulate gene expression of the following genes (represented by gene symbol): 25 YM stimulate the gene: Gene Symbol CXCL2, CSF2, 1L6, NFKBIZ, CXCL3, EGRI, CLDN14, ATF3, IL1A, CSF3, PTGS2, NFKBIZ, KRTAP4-9, TNFAIP3, ABL2, KRTAP4-7, MMP3, DUSP10, FOS, DUSP1, PPP1R15A, DDIT3, DUSP10, HECW2, DSCR1, SESN2, TSLP, SLC7A11, HES1, SESN2, CXCL1, TAGLN3, HBEGF, IER3, RAB2, P8, 1L8, GADD45A, LOC441461, 30 GEM, LIF, KLF6, MGC4504, CCL20, PRB1 /// PRB2, THRA /// NR1D1, ERN1, NECAP2, DKK3, GNAO1, NFKBIA, CREB5, CLDN1, CDKN1A, PRDM1, SERPINB2, CD274, FST, LOC401317, BIRC3, PMAIP1, BMP2, 1L24, BMP2, WHDC1L2, SGK, RND3, UPP1, C14orf34, ARID1B, KLF6, KLHL24, MAFF, IL12A, SAT, NSD1, JUNB, DUSP1, SLC3A2, ASNS, MAFF, PSAT1, CLTA, ZC3H12C, CLDN1, IL1B, ROBO4, 35 RARA, BCL6, SLC7A11, PDE4DIP, ZNF697, ATP2A2, ZFP36, REST, HDAC9, STAC2, LOC153222, ZC3H12A, SLC25A37, IL17C, TRIB3, CEBPB, PTX3, TRIB3, KIAA1718, WO 2009/117196 PCT/US2009/034115 56 ZNF385, TTMP, MGC5618, CSF2, DUSP5, SLC25A25, ADAMTS1, TFRC, SEC15L2, SCNN1A, HES1, LOC153222, C20orf72, ETS1, GDF15, KIAA1754, PACRG, PRSS22, TFRC, AQP2, STX3A, REM1, LIMK2, STC2, ISG20L1, BCL2A1, HES4, TJP3, SLC7A5, CEBPG, LILRB2 /// LILRB3, LOC389429, LLGL1, KLF6, CSNK1E, DUSP1, ICAM1, 5 PYY2, TPCN1, MFSD2, KIAA0690, SOD2, E2F7, GRIK5, PADI1, HIP1R, IRAK2, EIF1, CEBPG, GOS2, KIAA0690, NEDD4L, MXD1, TXNDC5, PERLD1, HIFlA, RDH13, CTH, ETS2, FAH, CLK4, RIMS4, FLJ12355, LDLR, WARS, IFRD1, LRCH4, SLC1A4, FST, PPIF, ARHGEF2, PMAIP1, PBEF1, C14orf159, ATF4, FLJ90119, TGFBR3, DDX21, MUC8, TNFSF7, SPTLC2, KBTBD8, CIAS1, KIAA0476, NFKB1, DES /// FAM48A, 10 ICAM1, INHBA, MARS, Clorfll3, GRK6, TCF2, SLC7A1, TNFRSF10B, IER2, TFRC, SOS2, CARS, HAB1 /// LOC442496, KLHL24, SQSTM1, GIT1, IRS2, SARS, TRIM25, JUN, YRDC, ETS1, CTH, ABL2, CD274, FZD8, EREG, PFDN2, TMEM63B, DYRK3, GARS, RASSF8, CAMTA2, HOXC8, AARS, TBX3, RRAGC, BCAP29, TNFRSF10B, MCL1, PALM2-AKAP2, TMEM22, ZNF548, PCBP2, SLC1A4, FSTL3, TA-PP2C, PIM3, 15 MAFG, NOL1, PEA15, ETS2, IQCG, BEX2, C12orf39, LDLR, VEGF, CCNL1, LOC440069, SNAPC1, SLC27A5, MARS, ICAM1, AXUD1, KCNIP2, LOC146177 /// FLJ40941, GOT1, Cllorf17 /// NUAK2, TTBK1, SNCA, NFRKB, GRB2, ADAMTS1, PALM2-AKAP2, CCNL1, JUN, SPRY4, SLC38A1, E2F7, MGC27165, IDS, SLC7A1, FLJ11021, KCNK5, GYPC, MYC, CACNG6, PHLDA1, INSIG1, FLJ13448, LOC202051, 20 GALNT10, TFEB, ABL2, MTHFD2, SERPINB8,TNPO2, MCF2L, SERTAD1, SPRY2, PHLDA1, SLC7A11, CXCL5, COMT, GTPBP2, RAB4B, ATXN7, OTUD5, VEGF, ADAMTS6, YARS, NAV3, SAMD4, C17orf32, SHMT2, CHIC2, ORAOV1, CREM, ALS2CL, AMIGO2, MGC19764, SFPQ, MGC11257, PLEKHM1, MMP28, SLC4A5, DNAJB9, ERRF11, FZD8, MGC4399, GUCA1B, ATP13A3, KIAA0020, XBP1, 25 ATP6V1B2, IGLV3-25, CHD4, GRB10, FLJ40089, CLDN19, NPC1, RIPK2, PLEKHF2, LOC283314, RSPO3, GSK3A, ANKRD11, WARS, GNPDA1, IGKC /// IGKV1-5, RCL1, C9orf9l, TIMM10, SLC1A4, ODC1, SLC38A1, EIF4EBP1, ZNF267, YRDC, CHD4, PER1, NFKBIE, INSIG1, FLJ11259, NCOA3, TNPO2, BAZ2A, SLC1A5, KRTAP2-1, PDE4DIP, EPB41L3, CITED2, JTV1, TA-PP2C, METRNL, BCL10, Clorfl9, PTP4A1, 30 PDE4DIP, CPSF1, TIMM10, IGSF21, TM4SF1, CDK6, BANP, PHLDA1, PAPPA2, MGC17337, TNFRSF19L, ADAMTS10, CBFB, HERPUD1, RTTN, FLJ13855, SYNPO, NAV2, FLJ34208, DDX10, C6orf66, LOC56902, CHMP1B, HIPK2, H3F3B, NAV3, ELL2, NSUN5C, PLAUR, UCK2, PBEF1, TP53BP2, TEX10, B3GNT5, USP36, INHBA, SPIRE1, CSTB, NSUN5C, TFPI2, 35 WO 2009/117196 PCT/US2009/034115 57 Our experiment disclosed that Xanifolia Y and ACH-Y inhibited genes expression of the following genes: FN1, ITGAV, LAMA4, LAMB2, LAMC1, LAMB1, LAMB1, LAMA4, LAMA5, LAMC1, LAMA2, LAMB1, LAMA3, SCAMPI, TICAM2, SCAMPI, TICAM2, SCAMPI, SCAMPI, CAMK2B, DL1, ICAM3,CEECAM1,ICAM5,SCAMP1, CAMK1G, 5 CAMSAP1, MCAM, CAMTA1, CKN1, ALCAM, DCAMKL2, CEACAM3, CAMK2D, CAMK2B, SCAMP5, CAMK4, NCAM1, CAMK2G, MYH9, MYH10, MYO1D, MYO5A, MYLK, MYO6, MYO5A, MYO1C, MYLK, MYO6, MYLC2PL, MYO10, MYO6, TPM3, MYO1C, BECN1, MYO1E, TPM3, M-RIP, MYO1B, MYO10, MYO5A, M-RIP, MYO10, MYL6, MYOHD1, BECN1, TPM4, MYLK, MYH10, MYOHD1, LOC221875, LOC402643, 10 MYO15B, LOCl 29285, MYH11, MYO1B, MYO1C, MYO9B, CDH13, CTNNAL1, CDH13, CDH12, CTNNB1, CDH5, CTNND1, CDH2, CTNNA1, CDH2, PCDHB16, CTNNA1, CELSR2, PCDHB6, PCDHB7, CTNND2, PCDHGC3, PCDHGB4, PCDHGA8, PCDHGA12, PCDHGC5, PCDHGC4, PCDHGB7, PCDHGB6, PCDHGB5, PCDHGB3, PCDHGB2, PCDHGB1, PCDHGA11, PCDHGA10, PCDHGA9, PCDHGA7, PCDHGA6, 15 PCDHGA5, PCDHGA4 , PCDHGA3 , PCDHGA2, PCDHGA1, CTNND1, CDH23, PCDHB12, PCDHB10, PCDH18, CDH20, PCDH9, PCDHGA12 , PCDHGA11, PCDHGA10, PCDHGA6, PCDHGA5, PCDHGA3, PCDH7, CDH18, CDH6, CCBE1, COL10A1, COL12A1, COL13A1, COL18A1, COL1A1, COL21A1, COL4A1, COL4A2, COL4A5, COL4A6, COL5A1, COL5A2, COL6A1, COL6A2, COL6A3, COL9A1, MMP9, 20 P4HA1, P4HA2, P4HB, PCOLCE, PCOLCE2, PCOTH, PLOD1, PLOD2, PLOD3, CIB1, ILK, ITGA2, ITGA3, ITGA4, ITGA6, ITGAV, ITGB1, ITGB1BP1, ITGB2, ITGB5, ITGBL1, TNC, EMILIN1, ICAM1, HSPG2, HPSE, HS2ST1,SDC2, Determination of gene expression by Real-time PCR method (Brilliant QPCR, 25 Agilent Technologies): The real-time polymerase chain reactions further confirm the results obtained from micro array analysis. The Real-time PCR results (shown below) confirmed that Compound Y3 and YM increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z WO 2009/117196 PCT/US2009/034115 58 Table 19: ANGPT2 DDIT3 LIF NFKB1Z % of control Control 100 100 100 100 Y3 300 213 163 142.9 YM 216 660 447 784.8 YM = Y3 without D = DMSO control Y = Y3 sugar Table 20: The experimental results confirmed that compound Y3 inhibit the gene 5 expression of adhesion proteins: ITGAV, TNC, COL1A1, FN1 and LAMA4 ITGAV TNC COL1A1 FN1 LAMA4 % of control Control 100 100 100 100 100 Y3 63.8 41.1 49.9 44.1 53.6 With the same method, we also confirmed that the compound YM inhibits the expression of adhesion proteins COL1A1, FN1 and LAMA4 WO 2009/117196 PCT/US2009/034115 59 Table 21: COL1A1 FN1 LAMA4 % of control Control 100 100 100 YM 42 72.8 81 ANGPT2 =angeopoietin 2, LIF = Leukemia inhibitory factor ITGAV = integrin alpha V, (cholinergic differentiation factor), TNC = Tenascin C, NFKB1 Z = nuclear factor of kappa light COL1 Al = collagen type 1 alpha 1, polypeptide gene enhancer in B-cells FN1 = fibronectin 1, inhibitor, zeta LAMA4 = laminin alpha 4, DDIT3 = DNA-damage-inducible transcript 3, Data obtained from our Microarray experiments disclose that Xanifolia Y modulates 5 gene expression.This invention provides compositions and methods for modulating the gene expression in cancer cells, wherein the modulating comprises of positive and negative regulation, wherein genes being modulatated are adhesion proteins; wherein modulation includes expression, production and secretion of adhesion proteins, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin , 10 vitronectin, collagen, laminin, cadherin, heparin, Glypican, tenascin, CD 54, CAM. This invention provides compositions and methods for modulating angiopoietins, wherein comprises positive regulating the angiopoietin 2, wherein comprises negative regulating angiopoietin 1. The composition and method of this invention comprises a triterpene wherein acylation group at carbon position 21 and/or 22 of the triterpene is necessary 15 for the function and are selected from angeloyl, acetyl, alkanoyl, and alkenoyl and acyl group. The sugar moiety (ies) at position 5 of the triterpene is important for enchancing activity of these compounds. Leptin is a promoter in breast cancer cells. The Xanifolia Y and YM inhibits the 20 expression of leptin. The thrombospondins are a family of multifunctional proteins. The family includes thrombospondins 1-5. Thrombospondin-1 TSP1 is a multifunctional, matricellular WO 2009/117196 PCT/US2009/034115 60 glycoprotein, containing interacting domains for a large variety of adhesion, migration and proliferation, angiogenesis and tumor cell metastasis. The insulin-like growth factor binding protein (IGFBP) is a multifunctional protein that 5 relate to metastasis, tumor growth and angiogenesis. Compounds in this application modulate gene expression of RAB3B, inhibiting metastasis, tumor growth and angiogenesis. The activation of cell migration and cancer cells metastasis requires the sensitive of 10 potassium channel. The results of the micro array experiment showed that compound Y and YM inhibit gene expression of family protein relate to potassium channel in ES2 cells. RAB3B is member RAS oncogene family protein. Compounds in this application 15 modulate gene expression of RAB3B, inhibiting metastasis, tumor growth and angiogenesis. In mild conditions, the saponin can be partially hydrolyzed into a mixture of products which are separated by HPLC. Specific partial hydrolysis of saponins can also be 20 achieved with enzymes. The glycosidases catalyze the hydrolysis of the glycosidic linkage. Galactosidase is an enzyme which catalyzes the hydrolysis of galactosides. The glucosidase is an enzyme which breaks glucose from saponin. Other enzyme examples are xylanases, lactase, amylase, chitinase, sucrase, maltase, and neuraminidase. 25 The sugar moiety of the triterpenoid saponin (example Xanifolia Y) can be removed by acid hydrolysis. The synthetic compound of ACH-Y is obtained. The ACH-Y is a triterpene with acyl groups but no sugar moiety. The acyl group of the saponin (example Xanifolia Y) can be removed by alkaline hydrolysis. A synthetic compound of AKOH-Y 30 can be obtained. The AKOH-Y is a pentacyclic triterpene with sugar moieties. A pentacyclic triterpene can be obtained by acid and alkaline hydroysis of saponin from natural source. A pentacyclic triterpene also can be obtained by other methods (Reference: Surendra et al., Rapid and Enantioselective Synthetic Approches to Germanicol and Other Pentacyclic Triterpenes). The pentacyclic triterpene with sugar 35 moieties can also be obtained with synthesis (Reference: Ple et al., Synthesis of L arabinopyranose containing hederagenin saponins). Acylation is the process of adding WO 2009/117196 PCT/US2009/034115 61 an acyl group to a compound. Friedel-Crafts reaction is an example of the process. An active compound can be obtained by acylating a pentacyclic triterpene. In an embodiment, acylating C21 and C22 of a pentacyclic triterpene gives an anticancer compound . In an embodiment, sugar moiety(s) at C3 can increase the activities of 5 pentacyclic triterpene, wherein the triterpene has acyl group(s), wherein the acyl group(s) may be at C21, 22, or 28. In an embodiment, a sugar moiety is at C21, 22, or 28, wherein the sugar moiety is substituted with 2 acyl groups. Reference in PCT/US/US05/319000, W020061029221, filed September 7, 2005, US1 1/289142 filed November 28, 2005) 10 Determination of cell growth of Leishmania parasites by MTT assay shows that Y10 is cytotoxic to Leishmania Major (promastigotes) with IC50 of 15ug/ml. IC 50 of Y is 15ug/ml, YO is 25ug/ml, Y1 is 23ug/ml, Y5 is 16ug/ml, Y7 is 18ug/ml, ACH-Y Is 30ug/ml, Mb5 is 15ug/ml, ACH-Mb5 is 18ug/ml, Z12 is 23ug/ml, and Bal is 15ug/ml 15 EXPERIMENTAL DETAILS Experiment details of herb extraction, analysis of extract components by HPLC, determination of the cell-growth activity effected by Xanifolia Y with cells derived from different human organs using MTT Assay, purification of the bioactive components from 20 plant extract, fractionation of plant extracts with FPLC, isolation of component Ys with preparative HPLC, determination of the chemical structure, cell experiments and animal studying are disclosed in PCT/US05/31900, U.S. Serial No. 11/289142, U.S. Serial 10/906303, U.S. Serial No. 11/131551 and U.S. Serial Nos. 11/683198, filed on March 7, 2007, PCT/US2007/077273, filed August 30, 2007, U.S. Serial No. 60/890380, filed on 25 February 16, 2007, U.S. Nos. 60/947,705, filed on July 3, 2007, PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008, the contents of which are incorporated herein by reference. Experiments 1-23 of PCT/US2008/002086, 1188-ALA-PCT, filed February 15, 2008 are incorporated herein by reference. 30 Experiment 1: Removal of the sugar moiety from saponin by acid hydrolysis 15 mg saponin was dissolved in 1 ml of Methanol. 1 ml of 2N HCI was then added. The mixture was refluxed in 80C water bath for 5 hours. The solution was then neutralized by adding 2 ml of 1 N NaOH (to final pH 4-6). The aglycone was then extracted with ethylacetate 3 ml x 2. The extracts were collected and pooled. Further 35 isolation of aglycone (sugar-removed saponin) was achieved by HPLC with isocratic elution of 80-100% acetonitrile.

WO 2009/117196 PCT/US2009/034115 62 Experiment 2: Removal of the acyl group by alkaline hydrolysis Methods: 20 mg of saponin was dissolved in 0.5 ml of 1 M NaOH. The solution was incubated in 80C water bath for 4 hours. It was cooled to room temperature before neutralized with 0.5 ml 1 N HCI (adjust pH to about 3). The mixture was extracted with 2 5 ml 1-butanol 3 times. The butanol fractions were collected and lyophilized. The hydrolyzed saponin with further purified with HPLC in a C-18 column eluted with 25% acetonitrile. Experiment 3: Analysis of genesis of blood vessel in xenograft tumor treated with 10 compound Y Methods: Athymic Nu/Nu mice (5-6 weeks old) are divided into two groups (1 and 2) with 5 animals in each group. On day 0, all mice were transplanted intra-peritoneally with one million ES2 (human ovarian cancer) cells. Animals were randomly divided into two groups: 15 Group 1: Control group. Animals did not receive drug-treatment. Group 2: Drug-treatment group. On days 10-15 and 18-22, animals received daily drug administration of Xanifolia-Y, by i.p. route at dosage of 2.5 mg/kg. Results: Animals showed high tumor burden after 18 days. Animals with high tumor 20 burden were euthanized and solid tumors were taken out from these mice (between 18 27 days). Tumor tissues fixed with formalin at room temperature. The fixed tissues were sectioned and stained with Haematoxylin and eosin (H&E). The red blood cells inside the micro blood vessels were identified under a microscope. Figure 1 shows that more blood vessels were observed in the control Group1 than those in the drug-treated 25 Group 2 Experiment 4: Determination of cell growth of Leishmania parasites by MTT assay. Leishmania parasites (Leishmania major: MRHO/SU/59/P/LV39) were grown in culture medium in a T75 flask at room temperature. Promastigotes of Leishmania major 30 (approximately 40 million per ml) were used in the experiment. 1.2 ml cell culture was transferred to a well of the 24-wells plate. Saponin Y1 0 (0.2 ml in medium) with different concentrations (final 6.25 -200 ug/ml) was added to culture and cells were grown for 1-5 days at room temperature. At the end of drug-treatment, 150 ul of MTT (5 mg/ml in PBS) was added to each well and incubated for 4 hours. Formazan formed in cells was 35 dissolved with DMSO and the OD at 490nm was determined by an ELISA reader.

WO 2009/117196 PCT/US2009/034115 63 Results: this experiment shows that Y10 is cytotoxic to Leishmania Major (promastigotes) with IC50 approximately equal to 15ug/ml. Experiments are repeated with Y, ACH-Y, AKOH-Y, Mb5, ACH-Mb5, AKOH-Mb5 and Bal. 5

Claims

1. A method for modulating adhesion protein of cells, inhibiting angiogenesis in tumor, modulating the gene expression, modulating the angiopoletin, enhancing an immune response, providing adjuvant activities, providing vaccine activities, or 5 inhibiting the metastasis of cancer cell in a subject, comprising contacting said subject with an effective amount of an isolated, purified or synthesized compound, or its salt, or ester thereof, selected from the formula: R 1 R 1 4 R 16 R 4 R 1 1 R 1 2 R2

13- R, R 5 0 R 3 R 9 R 1 0 , also named (1 E), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 10 alkyl, O-dibenzoyl, O-benzoyl, 0-alkanoyl, 0-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0-heterocylic, O-heteroraryl, and derivatives thereof; R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl 15 substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, O-dibenzoyl, O-benzoyl, 0 alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl 20 substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; R3 is H or OH; R8 is H or OH, preferably OH; R1 6 is H ,or R4 and R1 6 may form an oxygen bridge with divalent radical formula of -CH2-O-, CH(OH)-O- or C(=O)-0-, wherein the -0- may be replaced with 25 N- ; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; R5 is a hydrogen, heterocyclic or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, dose, lyxose, 30 mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; WO 2009/117196 PCT/US2009/034115 65 wherein R9, R1 0, R1 1, R1 2, R1 3, R1 4, R1 5 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, 5 R2 and R6 are compriseing a group selected from O-angeloyl, O-tigloyl, 0 senecioyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-aryl, 0-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, 10 acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; or wherein R4 is CH 2 R6, wherein R1 and R2 independently consists an 0 angeloyl group, or at least two of R1, R2 and R6 are O-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two O-angeloyls; or wherein R5 is/are the 15 sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises glucuronic acid, arabinose and 20 galactose; or wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, galacturonic acid, and a derivative or combination thereof; or wherein R5 is 3-P 0-{[(ca-L-rhamnopyranosyl-(1 ->2)]-a-L-rhamnopyranosyl--(1 -*2)-s-D galactopyranosyl--(1 ->3)]-[p-D- galactopyranosyl--(1 ->2)]- p-D 25 glucuronopyranosyl} 2. The method of claim 1, wherein at least one of R1 and R2 of the compound is selected from O-acetyl, O-angeloyl, O-tigloyl, O-senecioyl, O-dibenzoyl, and 0 benzoyl, or at least one of R1 and R2 is a sugar moiety substituted with two 30 groups selecting from acetyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl; R5 is a hydrogen or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group of glucose, galactose, arabinose and derivatives thereof, wherein the derivatives are acid, ester and salt. 35 3. The method of claim 1, wherein the modulating adhesion of cancer cell comprises inhibiting the secretion or expression of adhesion protein, wherein the WO 2009/117196 PCT/US2009/034115 66 adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, polyglycans, cadherin, heparin, tenascin, CD 54 and CAM; wherein the inhibiting protein expressed from genes, including ITGAV, TNC, COL1A1, FN1, LAMA4, family protein relate to potassium channel, RAB3B, 5 thrombospondin, insulin-like growth factor, G-protein and Glypican. 4. The method of claim 1, wherein the modulating adhesion protein comprises reducing the fibronectin for inhibiting the metastasis or growth of cancer cells, wherein the cancer is selected from breast, leukocyte, liver, ovarian, bladder, 10 prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancer. 5. The method of claim 1, wherein the inhibiting angiogenesis comprises modulating angiopoietin comprising angiopoietin 1, angiopoietin 2, angiopoietin 3, 15 angiopoietin 4, angiopoietin 5, angiopoietin 6 and angiopoietin 7; or wherein the angiopoietin is comprising angiopoietin-like 1, angiopoietin-like 2, angiopoietin like 3, angiopoietin-like 4, angiopoietin-like 5, angiopoietin-like 6 and angiopoietin-like 7; or wherein the modulating comprises positive and negative regulating; wherein modulating angiopoietin comprises stimulating the 20 angiopoietin 2 in order to inhibit angiogenesis; or wherein modulating angiopoietin comprises inhibiting the angiopoietin 1 in order to inhibit angiogenesis; or wherein modulating angiopoietin comprises inhibiting the angiopoietin-like 1; or wherein modulating angiopoietin comprises inhibiting the angiopoietin-like 4. 25 6. The method of claim 1, wherein the modulating gene expression includes increasing the expression of the protein phosphatase 1, dual specificity phosphatase 10; or increasing expression of the genes of ANGPT2, DDIT3, LIF and NFKB1Z. 30 7. The use of composition of claim 1, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound is having structure Xanifolia(Y), WO 2009/117196 PCT/US2009/034115 67 Y 3 0 OH 0 O H H H O 0H H HOH OH or chemical name: 3-0-[P-D galactopyranosyl (1 ->2)]-a-L-arabinofuranosy (1->3)--D-glucuronopyranosyl 21,22-0-diangeloyl-3p, 15x, 16ax, 21 P, 22x, 28-hexahydroxyolean-1 2-ene; 5 b) An isolated, purified or synthesized compound is having structure Xanifolia (Y1), OAc OH OH O H 0 OH OH or chemical name: 3-O-[p-D-galactopyranosyl (1 ->2)]-a-L-arabinofuranosyl (1 ->3)-j-D-glucuronopyranosyl-21-0-(3,4 diangeloyl)-ax-L-rhamnophyranosyl-22-O-acetyl-3 ,1 6ca, 21 P, 22x, 28 10 pentahydroxyolean-1 2-ene; c) An isolated, purified or synthesized compound is having structure Xanifolia (Y2), Y 2 O-i OH 0 OH H O H OH OH OH OH or chemical name: 3-0-[s-D-glucopyranosyl 15 (1 ->2)]-a-L-arabinofuranosy (1 ->3)- -D-glucuronopyranosyl-21,22-O-diangeloyl 3p, 15cx, 16ax, 21 P, 22x, 24P, 28-heptahydroxyolean-1 2-ene; d) An isolated, purified or synthesized compound is having structure Xanifolia (Y8), WO 2009/117196 PCT/US2009/034115 68 o-C 0" Y-8 ''o-c" OH 0 O HH OH HOO OH OH OH or chemical name: 3-O-[p8-glucopyranosyl (1 -2)]-a-arabinofuranosyl (1 -3)-#-glucuronopyranosyl-21, 22-O-diangeloyl-3p 16a, 21#, 22a, 24,#, 28-hexahydroxyolean-12-ene; 5 e) An isolated, purified or synthesized compound is having structure Xanifolia (Y9), -0 Y, "OH OAc "OH 0 CH HO O O OH I O OH HO OH O or chemical name: 3-O-[p galactopyranosyl (1 -2)]-a-arabinofuranosyl (1 -3)-#5-glucuronopyranosyl-21-0 (3,4-diangeloyl)- a-rhamnopyranosyl-28- 0-acetyl-3,#, 16 a, 21, 22a, 28 10 pentahydroxyolean-1 2-ene; and f) An isolated, purified or synthesized compound is having structure Xanifolia (Y10), 0-1 Y-10 "I -elo OH COOHo OH HO 0 -H~a OH , or chemical name: 15 3-0-[#-galactopyranosyl (1 -2)]-a-arabinofuranosyl (1 -3)-#6-glucuronopyranosyl 21, 22-O-diangeloyl-3p, 16a, 21 , 22a, 28-pentahydroxyolean-1 2-ene. g) An isolated, purified or synthesized compound is having structure Xanifolia (YO), WO 2009/117196 PCT/US2009/034115 69 31 CHO 25 26 C~O OH oo 7 0 24 23 2 7 H HO HO H HO o HO OH OH , or chemical name: 3-0-[p-D galactopyranosyl(1 ->2)]-ax-L-arabinofuranosyl(1 -3)-P-D-glucuronopyranosyl-21 O-angeloyl, 22-0-(2-methylpropanoyl)-3 , 15a, 16ax, 21 P, 22c, 28 hexahydroxyolean-1 2-ene, 5 h) An isolated, purified or synthesized compound is having structure Xanifolia (X), *'c 0 25 2 2 9 H 0 232 HO- HO HO OH or chemical name: 3-0-{[p-D galactopyranosyl (1 -2)]-[a-L-arabinofuranosyl (1 -3)]- -D-glucuronopyranoside butyl ester}-21-O-acetyl-22-O- angeloyl- 3,p,16a,21p8,22a,28-pentahydroxyolean 10 12-ene. i) An isolated, purified or synthesized compound is having structure (Y7), CH, 0 C HO HO HO OH , or chemical name: 3-O-[#-D galactopyranosyl-(1 ->2)]-a-L-arabinofuranosyl-(1 ->3)-1-D--glucuronopyranosyl 15 21-0-angeloyl-28--2-methylbutanoyl-33, 15 a, 16a, 218, 22a, 28 hexahydroxyolean-1 2-ene j) An isolated, purified or synthesized compound is having structure (ACH-Y): WO 2009/117196 PCT/US2009/034115 70 0-C 0 /O C OH 0 . OH OH HO k) An isolated, purified or synthesized compound is having structure: 3 29 H HH o-5 CH3 COOH 27 O23 CHOH OH OH, 0 0 OH O OH OHr OH OH H or chemical name: 5 3-O-[p-glucopyranosyl (1 ->2)]- p-arabinofuranosyl (1 ->4)-p- glucuronopyranosyl -21-0-angeloyl-22-0-acteyl-3p, 16a, 216, 22a, 24,p, 28-hexahydroxyolean-12 ene; (I) An isolated, purified or synthesized compound is having structure: O -C- TH 9 H 25 OH H o OHH COO 27 H O H 0 OOH 10 OH Y5 (n) An isolated, purified or synthesized compound is having structure: R R OHH OH HO 0 COOH OH 0 H 00 HO CH0 3 HO 0 HZ HO0 0 OH OH HO OH wherein R1, R2, are O(C=O)C(0H3)=CH(CH3), R3 is OH, R4 is OH (n) An isolated, purified or synthesized compound is having structure: WO 2009/117196 PCT/US2009/034115 71 H3 HHC CH3 H 3 C, CH, CH HC OH 0 0 3 HOA HOH R CH R HRR~ R, HC6, O /O OH HO O 0WeenR sOCOCC3=HC3,R CH, 1Ci COOH3 asnaedMb2 (p) An isolated, purified or synthesized compound is having structure: Rz R, 02 H HO COOH R13 H HO Co OH OH O OH wherein R is O(C=O)C(H3)=CH(CH3), R2 5 is O(c=O) H= H-C6H5, R3, R4 are OH, R6, R7, R8, R9, R2O,1 1, R12 are pH3, R1o3 is oH3, also named Mbl 2 (p) An isolated, purified or synthesized compound is having structure: 3^ 25 C s OH OH Z2 , OHH 3-0-[3 -D-galactopyranosyl(1-12)-2j- D-xyorasylop(1->3)- (1-D--3-D 1 0 ~ glucuronopyranosyl-21 -0-angeloyl, 22-0-atigloyl -3,16, 1, 212a, 2-,28 15pentahydroxyolean-1 2-ene; aedB sKc OHo 0, HO H OH0 3-O-[J-D-galactopyranosyl( (1 -*) )-p- D-xylopyranos yl (1 --3)-J3-D 10 glucuronopyranosyl-21-O-angeloyl, 22-0-tigeloyl -3, 1, 21P , 2-, 8 15pentahyd roxyo lean -1 2-ene; ae a1 8. A method for treating parasites in a subject, comprising contacting said subject with an effective amount of an isolated, purified or synthesized compound, or its salt, or ester thereof, selected from the formula: WO 2009/117196 PCT/US2009/034115 72 R 1 R 1 4 R 1 6 R 4 R 1 1 R 1 2 'R 1 3E R 5 0R R, R 10 , also named (1 E), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted 5 phenyl, O-aryl, O-acyl, 0-heterocylic, O-heteroraryl, and derivatives thereof; R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 alkyl, O-dibenzoyl, O-benzoyl, 0-alkanoyl, 0-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0-heterocylic, O-heteroraryl, and derivatives thereof; 10 R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, O-dibenzoyl, O-benzoyl, 0 alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, 0-heteroraryl, and derivatives thereof; R3 is H or OH; R8 is H or OH, preferably 15 OH; R1 6 is H ,or R4 and R1 6 may form an oxygen bridge with divalent radical formula of -CH2-0-, CH(OH)-O- or C(=0)-0-, wherein the -0- may be replaced with N- ; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; wherein the sugar moieties can not be 5, if the oxygen bridge is 20 formed between R4 and R16; R5 is a hydrogen, heterocyclic or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or 25 combination thereof; wherein R9, R10, R11, R12, R13, R14, R15 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO alkyl, COO-aryl, COO-heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0 heterocyclic, CH 2 0- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, R2 and R6 are compriseing a group selected 30 from O-angeloyl, O-tigloyl, O-senecioyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, 0 alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-aryl, O-acyl, O-heterocylic, WO 2009/117196 PCT/US2009/034115 73 0-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, 5 and a derivative thereof; or wherein R4 is CH 2 R6; wherein R1 and R2 independently consists an 0-angeloyl group, or at least two of R1, R2 and R6 are 0-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two 0 angeloyls; or wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, 10 fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises glucuronic acid, arabinose and galactose; or wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, 15 glucuronic acid, galacturonic acid, and a derivative or combination thereof; or wherein R5 is 3- -0-{[(a-L-rhamnopyranosyl-(1->2)]-u-L-rhamnopyranosyl- (1 ->2)-p-D- galactopyranosyl--(1 ->3)]-[p-D- galactopyranosyl--(1 ->2)]- p-D glucuronopyranosyl} 20 9. The method of claim 8, wherein at least one of R1 and R2 is selected from 0 acetyl, O-angeloyl, O-tigloyl, O-senecioyl, 0-dibenzoyl, and O-benzoyl, 0 alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, or at least one of R1 and R2 is a sugar moiety substituted with two groups selecting from acetyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl 0-alkanoyl substituted phenyl, 0 25 alkenoyl substituted phenyl; R5 is a hydrogen or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, arabinose and derivatives thereof, wherein the derivatives are acid, ester and salt. 10. The method of claim 8, wherein the antiparasitics comprise inhibiting 30 leishmaniases, amoebiasis, trypanosomiasis, toxoplasmosis or malaria. 11. The method of claim 8, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound is having structure Xanifolia(Y), WO 2009/117196 PCT/US2009/034115 74 Y 3 0 OH hIOH OHH H OH H HO OH or chemical name: 3-0-[p-D-galactopyranosyl (1 -2)]-a-L-arabinofuranosy (1 -3)-p-D-glucuronopyranosyl-21,22-O-diangeloyl 3P, 15cx, 16a, 21 P, 22cx, 28-hexahydroxyolean-1 2-ene; 5 b) An isolated, purified or synthesized compound is having structure Xanifolia (Y1), \/ Y 1 NOAc c OH H OOOH '0 H CH HO 0 OH 0 LOH o 0 O OH or chemical name: 3-0-[p-D-galactopyranosyl (1 ->2)]-a-L-arabinofuranosyl (1 ->3)- -D-glucuronopyranosyl-21-0-(3,4 diangeloyl)-ax-L-rhamnophyranosyl-22-O-acetyl-3p,1 6ca, 21 P, 22x, 28 10 pentahydroxyolean-1 2-ene; c) An isolated, purified or synthesized compound is having structure Xanifolia (Y2), OH 0 j, OH HO H O OH OH or chemical name: 3-O-[p-D-glucopyranosyl 15 (1 -2)]-a-L-arabinofuranosy (1 -3)-p-D-glucuronopyranosyl-21,22-0-diangeloyl 31, 15a, 16a, 21 P, 22ax, 24P, 28-heptahydroxyolean-1 2-ene; d) An isolated, purified or synthesized compound is having structure Xanifolia (Y8), WO 2009/117196 PCT/US2009/034115 75 - OC Y-8 ', OH 0 "iOH HOf OH L0 OH O OH or chemical name: 3-O-[p8-glucopyranosyl (1 -- 2)]-m-arabinofuranosyl (1 -3)-p8-glucuronopyranosyl-21, 22-O-diangeloyl-3, 16a, 21p6, 22a, 24p6, 28-hexahydroxyolean-12-ene; 5 e) An isolated, purified or synthesized compound is having structure Xanifolia (Y9), Y9 "OH OAc "OH 0 Oh H 0 HO S0Oor chemical name: 3- O-[,6-galactopyranosyl (1 - 2)]-m-arabinofuranosyl (1 -3)-)-glucuronopyranosyl-21-O-(3,4-diangeloyl)-a rhamnopyranosyl-28-O-acetyl-3p3, 16a, 21, 22a, 28-pentahydroxyolean-12-ene; 10 and f) An isolated, purified or synthesized compound is having structure Xanifolia (Y10), Y-10 "O OH 0 O OH HO 0 OH OH ,or chemical name: 15 3-0-[,6-galactopyranosyl (1 -*2)]-a-arabinofuranosyl (1 -3)-pi-glucuronopyranosyl 21, 22-0-diangeloyl-3p3, 16a, 21,6, 22a, 28-pentahydroxyolean-12-ene. g) An isolated, purified or synthesized compound is having structure Xanifolia (YO), WO 2009/117196 PCT/US2009/034115 76 H CH, 0 HC CH 21 22 cmH20H c "OH HO H o o 2 gC HO HO OH or chemical name: 3-O-[p-D galactopyranosyl(1 ->2)]-a-L-arabinofuranosyl(1 -- 3)-P-D-glucuronopyranosyl-21 O-angeloyl, 22-O-(2-methylpropanoyl)-3p, 15ax, 16x, 21 P, 22cc, 28 hexahydroxyolean-1 2-ene, 5 h) An isolated, purified or synthesized compound is having structure Xanifolia (X), 3CH 25 22 cc, H 6 OH OO o '23 HO HO H HO HO OH or chemical name: 3-0-{[p-D galactopyranosyl (1 ->2)]-[o-L-arabinofuranosyl (1 ->3)]-p-D-glucuronopyranoside butyl ester}-21-O-acetyl-22-0-angeloyl- 3p,16a,21p,22a,28-pentahydroxyolean 10 12-ene. i) An isolated, purified or synthesized compound is having structure (Y7), CCc HO HO HOOO 00 OH OH or chemical name: 3-O-[#-D galactopyranosyl-(1 -- 2)]-a-L-arabinofuranosyl-(1 -- 3)-f-D--glucuronopyranosyl 15 21-O-angeloyl-28-0-2-methylbutanoyl-3#, 15 a, 16a, 21P, 22a, 28 hexahydroxyolean-1 2-ene j) An isolated, purified or synthesized compound is having structure (ACH-Y): 20 .O-C II O H ol "OH HO. WO 2009/117196 PCT/US2009/034115 77 k) An isolated, purified or synthesized compound is having structure: 3 29 CH CH,0--0 25 2 CH0 COOH 27 23OHO 0, 0 0H OH .H OH or chemical name: 3-0-[#-glucopyranosyl (1 -*2)]- #-arabinofuranosyl (1 -4)--glucuronopyranosyl 21 -O-angeloyl-22-0-acteyl-3,#, 16a, 21#6, 22a, 24#8, 28-hexahydroxyolean-12 5 ene; I) 29 " O C 0,0 25 2 , C 0 H H, OH OHO HO H 0 10 0 OH 10 m) .R44 R, 0 H OH HOOH HO 0 0 000H Q OH 00 OhO HO C, 0 HO ) 0H ~~OH HO OH wherein R1, R2, are O(C=O)C(CH3)=CH(CH3), R3 is OH, R4 is OH WO 2009/117196 PCT/US2009/034115 78 (n) H3 H HC CH 3 CH 3 H 3 C H 'OH 0 CH 3 H HO 3 HO H 3 C OH 3 ACH-Mb5 (0) 33 3' 29 CH 3 H C 25 26 CH CH aO COOH 2 0 2 '2 5 OH 7 O HO HO H OH 5 3-0-[-D-galactopyranosyl(1 -- 2)]-p- D-xylopyranosyl (1 -- 3)-p-D glucuronopyranosyl-21-0-angeloyl, 22-0-angeloyl-3p, 15a, 21 P, 22a, 28 pentahydroxyolean-1 2-ene, named Ba 1; (p) OHC HOH f 20 H C HO HO OH -Ha OH OH Z12, 10 3-O-[p-D-galactopyranosyl(1 ->2)]-P- D-xylopyranosyl (1 ->3)-p-D glucuronopyranosyl-21-0-angeloyl, 22-0- tigloyl -3p, 16a, 21 P, 22a, 28 pentahydroxyolean-1 2-ene; 12. The method of claim 1, wherein the expression of the following genes is inhibited 15 (represented by gene symbol): AKR1 C3, SLC35A3, NEK9, CAV1, USP11, KRT7, TGM2, NCSTN, COG6, WDR4, GPAA1, GUSB, UBAP2L, NMT2, C9orf1O, KIAA0251, BTD, EMP1, KRT18, OS9, CPSF1, PSMD1, RNPEP///UBE2V1 /// Kua // Kua-UEV, NAGA, PARVA, HYOU1, ARMC4, APEH, BTD, FER1 L3, CFH /// CFHL1, COL5A2, 20 EFEMP1, COL18A1, HSDL2, NUP188, IDS, PLOD1, CPM, SPTAN1, LAMP2, ARNTL2, PLOD2, KDELR3, KIAA0586, SMARCA1, PRSS23, PTPRJ, LEPREL1, H2AFV, CAD, URB, CPNE3, DKFZP586JO619, SERPINB7, CNAP1, EEF2K, WO 2009/117196 PCT/US2009/034115 79 IKBKAP, SLC25A21, KDELR3, PDIA6, CAV2, COL4A2, MAGED2, PHF19, OACT2, JAG1, FAM62A, KDELR3, PIK4CA, USP5, ZDHHC20, H2AFV, PTPRF, PEG10, P4HA1, MAGED2, PRSS23, PTPRF, CHRDL1, C6orf65, APLP2, EXT2, COPG, SKIV2L, PDIA4, MYH9, SEC31 L1, GANAB, COL5A1, ZNF185, DDB1, 5 HDLBP, AP2B1, TSC2, IPO4, FLNA, TLN1, PRKDC, COL6A3, NTNG1, LEPR, RGS4, FN1, GPC6, LEPR, RGS4,IGFBP3; or wherein the expression of the following genes are stimulated (represented by gene symbol): P8, KRTAP4-7, DUSP10, CLDN14, ANGPT2, DUSP10, GDF15, GPNMB, HDAC9, HECW2, C14orf78, UPP1, PPP1R15A, PLEKHM1, STX3A, ANGPT2, 10 SQSTM1, RHOQ, STC2, PPP1R15A, LOC286044, ATF3, HMOX1, CXCL2, CD33L3, LRRC8E, SESN2, LIF, TFP12, KIAA1706, RRAGC, DDIT3, DYRK3, CTNS, GPNMB, CEBPB, CCL20, AMIGO2, KIAA1462, HSPBAP1, EVC, CLN8, ABL2, SGEF, MCTP1, IRS2, C14orfl09, TNFAIP3, RND3, ZFHX1B, LHFPL2, SNF1 LK, SLC3A2, NAV2, SPOCD1, TFP12, EV12A, ST3GAL6, CSTB, ROBO4, 15 GNPDA1, GEM, IRS2, HMGA2, PALM2-AKAP2, BR13, KIAA1754, VDR, NEU1, INSIG1, C17orf32, ABL2, PALM2-AKAP2, MTERFD3, ZNF697, NFKBIZ, BCL6, THRAP1, MGC5618, ADAMTS1, MAFG, NPC2, CITED2, TRIB3, ZCCHC9, RNU17D, CITED2, RRS1, NSUN5C, PBX2, RG9MTD1, SGSH, INSIG1, MGC16291, RAB9A, ARMCX6, SERPINB2, ATP6V1B2, DKFZP564I1171, 20 ATP6VOE, HSPC196, MRPS30, ARMCX1, LOC339229, ANKRD1 1, C9orf103, PSEN2, ADAMTS1, SNAPC1, RNF25, ZNF278, TGFBI, UAP1L1, PDE4DIP, MGC19764, TMEM60, CEP4, KIAA1211, DDX20, CSRP2BP, ZNF690, TRIO, CLTA, ATP6VOE, RAB32, MRPS31, LOC90693, ATP6V1C1, CBLL1, YTHDF2, FLJ14466, ARL10C, BCL2A1; or wherein the expression of the following genes 25 are stimulated (represented by gene symbol): CXCL2, CSF2, 1L6, NFKBIZ, CXCL3, EGR1, CLDN14, ATF3, IL1A, CSF3, PTGS2, NFKBIZ, KRTAP4-9, TNFAIP3, ABL2, KRTAP4-7, MMP3, DUSP10, FOS, DUSP1, PPP1R15A, DDIT3, DUSP10, HECW2, DSCR1, SESN2, TSLP, SLC7A11, HES1, SESN2, CXCL1, TAGLN3, HBEGF, IER3, RAB2, P8, 1L8, GADD45A, LOC441461, GEM, 30 LIF, KLF6, MGC4504, CCL20, PRB1 /// PRB2, THRA /// NR1 D1, ERN1, NECAP2, DKK3, GNAO1, NFKBIA, CREB5, CLDN1, CDKN1A, PRDM1, SERPINB2, CD274, FST, LOC401317, BIRC3, PMAIP1, BMP2, 1L24, BMP2, WHDC1L2, SGK, RND3, UPP1, C14orf34, ARID1B, KLF6, KLHL24, MAFF, IL12A, SAT, NSD1, JUNB, DUSP1, SLC3A2, ASNS, MAFF, PSAT1, CLTA, 35 ZC3H12C, CLDN1, IL1B, ROBO4, RARA, BCL6, SLC7A11, PDE4DIP, ZNF697, ATP2A2, ZFP36, REST, HDAC9, STAC2, LOC1 53222, ZC3H12A, SLC25A37, WO 2009/117196 PCT/US2009/034115 80 ILl 7C, TRIB3, CEBPB, PTX3, TRIB3, KIAA1 718, ZNF385, TTMP, MGC5618, CSF2, DUSP5, SLC25A25, ADAMTS1, TFRC, SEC15L2, SCNN1A, HES1, LOC153222, C20orf72, ETS1, GDF15, KIAA1754, PACRG, PRSS22, TFRC, AQP2, STX3A, REM1, LIMK2, STC2, ISG20L1, BCL2A1, HES4, TJP3, SLC7A5, 5 CEBPG, LILRB2 /// LILRB3, LOC389429, LLGL1, KLF6, CSNK1 E, DUSP1, ICAM1, PYY2, TPCN1, MFSD2, KIAA0690, SOD2, E2F7, GRIK5, PAD11, HIP1 R, IRAK2, EIF1, CEBPG, GOS2, KIAA0690, NEDD4L, MXD1, TXNDC5, PERLD1, HIFlA, RDH13, CTH, ETS2, FAH, CLK4, RIMS4, FLJ12355, LDLR, WARS, IFRD1, LRCH4, SLC1A4, FST, PPIF, ARHGEF2, PMAIP1, PBEF1, 10 Cl4orf159, ATF4, FLJ90119, TGFBR3, DDX21, MUC8, TNFSF7, SPTLC2, KBTBD8, CIAS1, KIAA0476, NFKB1, DES /// FAM48A, ICAM1, INHBA, MARS, Clorf1 13, GRK6, TCF2, SLC7A1, TNFRSF1OB, IER2, TFRC, SOS2, CARS, HAB1 /// LOC442496, KLHL24, SQSTM1, GIT1, IRS2, SARS, TRIM25, JUN, YRDC, ETS1, CTH, ABL2, CD274, FZD8, EREG, PFDN2, TMEM63B, DYRK3, 15 GARS, RASSF8, CAMTA2, HOXC8, AARS, TBX3, RRAGC, BCAP29, TNFRSF10B, MCL1, PALM2-AKAP2, TMEM22, ZNF548, PCBP2, SLC1A4, FSTL3, TA-PP2C, PIM3, MAFG, NOL1, PEA-15, ETS2, IQCG, BEX2, C12orf39, LDLR, VEGF, CCNL1, LOC440069, SNAPC1, SLC27A5, MARS, ICAM1, AXUD1, KCNIP2, LOC146177/// FLJ40941, GOT1, Cl1orf17 /// NUAK2, TTBK1, 20 SNCA, NFRKB, GRB2, ADAMTS1, PALM2-AKAP2, CCNL1, JUN, SPRY4, SLC38A1, E2F7, MGC27165, IDS, SLC7A1, FLJ11021, KCNK5, GYPC, MYC, CACNG6, PHLDA1, INSIG1, FLJ13448, LOC202051, GALNT10, TFEB, ABL2, MTHFD2, SERPINB8,TNPO2, MCF2L, SERTAD1, SPRY2, PHLDA1, SLC7Al1, CXCL5, COMT, GTPBP2, RAB4B, ATXN7, OTUD5, VEGF, ADAMTS6, YARS, 25 NAV3, SAMD4, C17orf32, SHMT2, CHIC2, ORAOV1, CREM, ALS2CL, AMIGO2, MGC1 9764, SFPQ, MGC11257, PLEKHM1, MMP28, SLC4A5, DNAJB9, ERRFI1, FZD8, MGC4399, GUCA1B, ATP13A3, KIAA0020, XBP1, ATP6V1B2, IGLV3-25, CHD4, GRB10, FLJ40089, CLDN19, NPC1, RIPK2, PLEKHF2, LOC283314, RSPO3, GSK3A, ANKRD11, WARS, GNPDA1, IGKC // 30 IGKV1-5, RCL1, C9orf91, TIMM10, SLC1A4, ODC1, SLC38A1, EIF4EBP1, ZNF267, YRDC, CHD4, PER1, NFKBIE, INSIG1, FLJ11259, NCOA3, TNPO2, BAZ2A, SLClA5, KRTAP2-1, PDE4DIP, EPB41L3, CITED2, JTV1, TA-PP2C, METRNL, BCL10, C1orfl9, PTP4A1, PDE4DIP, CPSF1, TIMM10, IGSF21, TM4SF1, CDK6, BANP, PHLDA1, PAPPA2, MGC17337, TNFRSF19L, 35 ADAMTS10, CBFB, HERPUD1, RTTN, FLJ13855, SYNPO, NAV2, FLJ34208, DDX10, C6orf66, LOC56902, CHMP1B, HIPK2, H3F3B, NAV3, ELL2, NSUN5C, WO 2009/117196 PCT/US2009/034115 81 PLAUR, UCK2, PBEF1, TP53BP2, TEX10, B3GNT5, USP36, INHBA, SPIRE1, CSTB, NSUN5C, TFPI2; or wherein the expression of the following genes is inhibited: FN1, ITGAV, LAMA4, LAMB2, LAMC1, LAMB1, LAMB1, LAMA4, LAMA5, LAMC1, LAMA2, LAMB1, LAMA3, SCAMPI, TICAM2, SCAMPI, 5 TICAM2, SCAMPI, SCAMPI, CAMK2B, DL1, ICAM3,CEECAM1,ICAM5,SCAMP1, CAMK1G, CAMSAP1, MCAM, CAMTA1, CKN1, ALCAM, DCAMKL2, CEACAM3, CAMK2D, CAMK2B, SCAMP5, CAMK4, NCAM1, CAMK2G, MYH9, MYH10, MYO1D, MYO5A, MYLK, MYO6, MYO5A, MYO1C, MYLK, MYO6, MYLC2PL, MYO10, MYO6, TPM3, MYO1C, BECN1, 10 MYO1E, TPM3, M-RIP, MYO1B, MYO10, MYO5A, M-RIP, MYO10, MYL6, MYOHD1, BECN1, TPM4, MYLK, MYH10, MYOHD1, LOC221875, LOC402643, MYO15B, LOC129285, MYH11, MYO1B, MYO1C, MYO9B, CDH13, CTNNAL1, CDH13, CDH12, CTNNB1, CDH5, CTNND1, CDH2, CTNNA1, CDH2, PCDHB16, CTNNA1, CELSR2, PCDHB6, PCDHB7, CTNND2, PCDHGC3, 15 PCDHGB4, PCDHGA8, PCDHGA12, PCDHGC5, PCDHGC4, PCDHGB7, PCDHGB6, PCDHGB5, PCDHGB3, PCDHGB2, PCDHGB1, PCDHGA11, PCDHGA10, PCDHGA9, PCDHGA7, PCDHGA6, PCDHGA5, PCDHGA4, PCDHGA3, PCDHGA2, PCDHGA1, CTNND1, CDH23, PCDHB12, PCDHB10, PCDH18, CDH20, PCDH9, PCDHGA12, PCDHGA11, PCDHGA10, PCDHGA6, 20 PCDHGA5, PCDHGA3, PCDH7, CDH18, CDH6, CCBE1, COL1OA1, COL12A1, COL13A1, COL18A1, COL1Al, COL21A1, COL4A1, COL4A2, COL4A5, COL4A6, COL5A1, COL5A2, COL6A1, COL6A2, COL6A3, COL9A1, MMP9, P4HA1, P4HA2, P4HB, PCOLCE, PCOLCE2, PCOTH, PLOD1, PLOD2, PLOD3, CIB1, ILK, ITGA2, ITGA3, ITGA4, ITGA6, ITGAV, ITGB1, ITGB1BP1, 25 ITGB2, ITGB5, ITGBL1, TNC, EMILIN1, ICAM1, HSPG2, HPSE, HS2ST1,SDC2, WO 2009/117196 PCT/US2009/034115 82 AMENDED CLAIMS received by the International Bureau on 22 July 2009 (22.07.2009) 13. A method for modulating the secretion or expression of adhesion protein of cells, modulating the gene expression, modulating the secretion or expression of 5 angiopoletin, enhancing an immune response, providing adjuvant activities, providing vaccine activities, or inhibiting the metastasis of cancer cell in a subject, comprising contacting said subject with an effective amount of an isolated, purified or synthesized compound, or its salt, or ester thereof, selected from the formula: R, R 1 4 R 1 6 R 4 R 1 1 R 12 R 1 3 ' R 5 0 R 3 10 R, R10 ,also named (1 E), wherein R1 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, 0-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; 15 R2 is selected from hydrogen, hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 alkyl, O-dibenzoyl, O-benzoyl, 0-alkanoyl, 0-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, 0-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from 20 hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, O-dibenzoyl, O-benzoyl, 0 alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; R3 is H or OH; R8 is H or OH, preferably OH; 25 R1 6 is H ,or R4 and R1 6 may form an oxygen bridge with divalent radical formula of -CH2-O-, CH(OH)-O- or C(=O)-0-, wherein the -0- may be replaced with NH- ; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; R5 is a hydrogen, heterocyclic or sugar moiety(ies), wherein the sugar 30 moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 83 mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; wherein R9, R1 0, R1 1, R1 2, R1 3, R1 4, R1 5 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO 5 heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, R2 and R6 are compriseing a group selected from O-angeloyl, O-tigloyl, 0 senecioyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, and 10 derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; or wherein R4 is CH 2 R6, wherein R1 and R2 independently consists an 0 15 angeloyl group, or at least two of R1, R2 and R6 are O-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two O-angeloyls; or wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, 20 glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises glucuronic acid, arabinose and galactose; or wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, galacturonic acid, and a derivative or combination thereof; or wherein R5 is 3-0 25 O-{[(ax-L-rhamnopyranosyl-(1 ->2)]--L-rhamnopyranosyl--(1 ->2)-P-D galactopyranosyl--(1 ->3)]-[p-D- galactopyranosyl--(1 ->2)]- -D glucuronopyranosyl}

14. The method of claim 13, wherein at least one of R1 and R2 of the compound is 30 selected from O-acetyl, O-angeloyl, O-tigloyl, O-senecioyl, O-dibenzoyl, and 0 benzoyl, or at least one of R1 and R2 is a sugar moiety substituted with two groups selecting from acetyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl; R5 is a hydrogen or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group of glucose, galactose, arabinose and derivatives thereof, wherein 35 the derivatives are acid, ester and salt. AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 84

15. The method of claim 13, wherein the modulating secretion or expression of adhesion of cancer cell comprises inhibiting the secretion or expression of adhesion protein, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, polyglycans, cadherin, heparin, 5 tenascin, CD 54 and CAM; wherein the inhibiting protein expressed from genes, including ITGAV, TNC, COL1A1, FN1, LAMA4, family protein relate to potassium channel, RAB3B, thrombospondin, insulin-like growth factor, G-protein and Glypican. 10 16. The method of claim 13, wherein the modulating the secretion or expression of adhesion protein comprises reducing the secretion or expression of fibronectin for inhibiting the metastasis or growth of cancer cells, wherein the cancer is selected from breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, esophagus, testis, 15 spleen, kidney, lymph, pancreas, stomach and thyroid cancer.

17. The method of claim 13, wherein the modulating secretion or expression of angiopoietin comprising angiopoietin 1, angiopoietin 2, angiopoietin 3, angiopoietin 4, angiopoietin 5, angiopoietin 6 and angiopoietin 7; or wherein the 20 angiopoietin is comprising angiopoietin-like 1, angiopoietin-like 2, angiopoietin like 3, angiopoietin-like 4, angiopoietin-like 5, angiopoietin-like 6 and angiopoietin-like 7; or wherein the modulating secretion or expression of angiopoietin comprises positive and negative regulating; wherein modulating angiopoietin comprises stimulating secretion or expression of the angiopoietin 2 25 in order to inhibit angiogenesis; or wherein modulating angiopoietin comprises inhibiting secretion or expression of the angiopoietin 1 in order to inhibit angiogenesis; or wherein modulating angiopoietin comprises inhibiting secretion or expression of the angiopoietin-like 1; or wherein modulating angiopoietin comprises inhibiting the secretion or expression of angiopoietin-like 4. 30

18. The method of claim 13, wherein the modulating gene expression includes increasing the expression of the protein phosphatase 1, dual specificity phosphatase 10; or increasing expression of the genes of ANGPT2, DDIT3, LIF and NFKB1Z. 35 AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 85

19. The method of claim 13, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound is having structure Xanifolia(Y), OH 0 H 0 COOH 6 H O HOH OHH H H OH or chemical name: 3-0-[-D galactopyranosyl (1->2)]-a-L-arabinofuranosy (1->3)--D-glucuronopyranosyl 5 21,22-0-diangeloyl-3s, 15a, 16a, 21s, 22a, 28-hexahydroxyolean-12-ene; b) An isolated, purified or synthesized compound is having structure Xanifolia (Y2), - OA OH OH HO OH--O H OH 00 O O H or chemical name: 3-0-[P-D-galactopyranosyl 10 (1 ->2)]-a-L-arabinofuranosyl (1 ->3)--D-glucuronopyranoyranosyl-21-0-(3,4 diangeloyl)-ax-L-rhamnophyranosyl-22-O-acetyl-3 ,1 6a, 21 P, 22ax, 28 pentahyd roxyo lean- 1 2-ene; c) An isolated, purified or synthesized compound is having structure Xanifolia 15 (Y2), A H H H0 HO OOH or chemical name: 3-0-[P-D-glucopyranosyl (1->2)]-ax-L-arabinofuranosy (1->3)-5-D-glucuronopyranosyl-21,22-O-diangeloyl 3@, 15ax, 16a, 21@P, 22ax, 24P, 28-heptahydroxyolean-1 2-ene; 20 d) An isolated, purified or synthesized compound is having structure Xanifolia (Y8), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 86 O-C 0" Y-8 - ''''O -c OH 0 'OH HO O OH HO OH OH OH or chemical name: 3-0-[-glucopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-p-glucuronopyranosyl-21, 22-O-diangeloyl-3p 16a, 21p6, 22a, 246, 28-hexahydroxyolean-1 2-ene; 5 e) An isolated, purified or synthesized compound is having structure Xanifolia (Y9), -0 Y 9 ""OH OAc "OH HO O 0 OH 0 00 O HOO tOH o OH or chemical name: 3-0-[# galactopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-,6-glucuronopyranosyl-21-0 (3,4-diangeloyl)- a-rhamnopyranosyl-28- 0-acetyl-3,#, 16 a, 21, 22a, 28 10 pentahydroxyolean-1 2-ene; and f) An isolated, purified or synthesized compound is having structure Xanifolia (Y10), Y-10 " -/O-e,-- OH 0 COOH OH'* HOH H OH , or chemical name: 15 3-0-[p-galactopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-pi-glucuronopyranosyl 21, 22-0-diangeloyl-36, 16a, 21, 22a, 28-pentahydroxyolean-1 2-ene. g) An isolated, purified or synthesized compound is having structure Xanifolia (YO), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 87 30 29 0 Ce 2H 2 c o ,,CH, o I OOH 7 H2OH HO Ho H OH OH or chemical name: 3-O-[P-D galactopyranosyl(1 ->2)]-a-L-arabinofuranosyl(1 ->3)-p-D-glucuronopyranosyl-21 O-angeloyl, 22-0-(2-methylpropanoyl)-3p, 15ca, 16ca, 21 P, 22ca, 28 hexahydroxyolean-1 2-ene, 5 h) An isolated, purified or synthesized compound is having structure Xanifolia (X), 3 22 C 0 0 2 23 27 HO OH , or chemical name: 3-O-{[p6-D galactopyranosyl (1->2)]-[a-L-arabinofuranosyl (1 ->3)]- -D-glucuronopyranoside butyl ester}-21-O-acetyl-22-0- angeloyl- 3,p,16 a,21,8,22 a,28-pentahydroxyolean 10 12-ene. i) An isolated, purified or synthesized compound is having structure (Y7), 2 H H 21 2 - 0H C20 oH COOH 2 HO H HO HOH OH or chemical name: 3-0-[#-D galactopyranosyl-(1 -- 2)]-a-L-arabinofuranosyl-(1 ->3)-3-D--glucuronopyranosyl 15 21-0-angeloyl-28-0-2-methylbutanoyl-33, 15 a, 16a, 210, 22a, 28 hexahydroxyolean-1 2-ene j) An isolated, purified or synthesized compound is having structure (ACH-Y): . -- c 'o OH C 2 "'OH OH H . 9O 20 HO AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 88 k) An isolated, purified or synthesized compound is having structure: 2CH N .11" ' CH, 0DH COOH 27 23 CH2OH O OH 00 OH OH o O OH OH OH or chemical name: 3-O-[f-glucopyranosyl (1 ->2)]- p-arabinofuranosyl (1 ->4)-,6- glucuronopyranosyl 5 -21-0-angeloyl-22-0-acteyl-3p, 16a; 216, 22a, 246, 28-hexahydroxyolean-12 ene; (I) An isolated, purified or synthesized compound is having structure: HO" 2,2 OH Y HO OHO IHOH o H HO O OH Y5 1 0 (in) An isolated, purified or synthesized compound is having structure: R4 -,'R2 R, OH HO O 0 COOH "R HOH 00 H4 0 HO 1H C OH HO OH wherein R, R2, are O(C=O)C(CH3)=CH(CH3), R3 is OH, R4 is OH (n) An isolated, purified or synthesized compound is having structure: AOH 0 0 0 H3C CHH 2 0 2OH O H 2 CH, HO H 2 C CAGH-Mb5 15 (o) An isolated, purified or synthesized compound is having structure: AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 89 OH RR HO O0 RR1 OH OH HO H O HO OH HO OH ,wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 is O(C=O)CH=CH-C6H5, R3, R4 are OH, R6, R7, R8, R9, R10, R11, R12 are CH3, R13 is COOCH3, also named Mbl2 (p) An isolated, purified or synthesized compound is having structure: HO 5 OH 3-0-[P-D-galactopyranosyl (1 ->2)]-p- D-xylopyranosyl (1 - 3)-p-D glucuronopyranosyl-21 -0-angeloyl, 22-O-angeloyl-3, 15aX, 21 P, 22a, 28 pentahydroxyolean-12-ene, named Ba 1; HO HOs OH Z12, 10 3-0-[P-D-galactopyranosyl(1 -2)]-p- D-xylopyranosyl (1 ->3)-p-D glucuronopyranosyl-21-0-angeloyl, 22-0- tigloyl -3s, 16a, 21sP, 22a, 28 pentahydroxyolean-1 2-ene;

20. A method for treating parasites in a subject, comprising contacting said subject 15 with an effective amount of an isolated, purified or synthesized compound, or its salt, or ester thereof, selected from the formula: R, R1 4 Ri R16 R 4 R, R 14 R11 R12 ''R2 R, 138 R 5 0 R 3 R, R 1 0 , also named (1 E), wherein R1 is selected from hydrogen, hydroxyl, 0-angeloyl, 0-tigloyl, O-senecioyl, 0 alkyl, 0-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, 0-benzoyl alkyl AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 90 substituted O-alkanoyl, O-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, O-aryl, 0-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; R2 is selected from hydrogen, hydroxyl, 0-angeloyl, 0-tigloyl, O-senecioyl, 0 alkyl, 0-dibenzoyl, 0-benzoyl, 0-alkanoyl, O-alkenoyl, O-benzoyl alkyl 5 substituted O-alkanoyl, O-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, O-aryl, 0-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0-dibenzoyl, O-benzoyl, 0 alkanoyl, O-alkenoyl, 0-benzoyl alkyl substituted 0-alkanoyl, 0-alkanoyl 10 substituted phenyl, 0-alkenoyl substituted phenyl, O-aryl, 0-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; R3 is H or OH; R8 is H or OH, preferably OH; R1 6 is H or R4 and R1 6 may form an oxygen bridge with divalent radical formula of -CH2-0-, CH(OH)-O- or C(=O)-O-, wherein the -0- may be replaced with 15 N- ; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; wherein the sugar moieties can not be 5, if the oxygen bridge is formed between R4 and R16; R5 is a hydrogen, heterocyclic or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, 20 gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; wherein R9, R10, R11, R12, R13, R14, R15 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO alkyl, COO-aryl, COO-heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0 25 heterocyclic, CH 2 O- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, R2 and R6 are compriseing a group selected from O-angeloyl, O-tigloyl, O-senecioyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, 0 alkenoyl, 0-benzoyl alkyl substituted 0-alkanoyl, 0-aryl, 0-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a 30 sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; or wherein R4 is CH 2 R6; wherein R1 and R2 independently consists an O-angeloyl group, or at least two of R1, R2 and R6 are 35 O-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two 0 angeloyls; or wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 91 fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises glucuronic acid, arabinose and galactose; or wherein R5 is/are sugar moiety(ies) 5 selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, galacturonic acid, and a derivative or combination thereof; or wherein R5 is 3-j-O-{[(a-L-rhamnopyranosyl-(1->2)]-a-L-rhamnopyranosyl- (1 ->2)-p-D- galactopyranosyl--(1 ->3)]-[P-D- galactopyranosyl--(1 ->2)]- P-D glucuronopyranosyl} 10

21. The method of claim 20, wherein at least one of R1 and R2 is selected from 0 acetyl, 0-angeloyl, O-tigloyl, 0-senecioyl, 0-dibenzoyl, and O-benzoyl, 0 alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, or at least one of R1 and R2 is a sugar moiety substituted with two groups selecting from acetyl, 15 angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl 0-alkanoyl substituted phenyl, 0 alkenoyl substituted phenyl; R5 is a hydrogen or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, arabinose and derivatives thereof, wherein the derivatives are acid, ester and salt. 20 22. The method of claim 20, wherein the antiparasitics comprise inhibiting leishmaniases, amoebiasis, trypanosomiasis, toxoplasmosis or malaria.

23. The method of claim 20, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound is having structure Xanifolia(Y), Y 3 / Oi OH I'OH H H OOH O H HH 0 H 25 H or chemical name: 3-0-[P-D-galactopyranosyl (1 ->2)]-a-L-arabinofuranosy (1 ->3)- -D-glucuronopyranosyl-21,22-0-diangeloyl 3P, 15a, 16a, 21 P, 22ax, 28-hexahydroxyolean-1 2-ene; b) An isolated, purified or synthesized compound is having structure Xanifolia 30 (Yi), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 92 Y 1 HH H OH O H c-OOO H CH HO -,o \_ I O C1H or chemical name: 3-0-[B-D-galactopyranosyl (1 ->2)]-c-L-arabinofuranosyl (1 ->3)- -D-glucuronopyranosyl-21-O-(3,4 diangeloyl)-ax-L-rhamnophyranosyl-22-O-acetyl-3B,1 6ax, 21 B, 22a, 28 pentahydroxyolean-1 2-ene; 5 c) An isolated, purified or synthesized compound is having structure Xanifolia (Y2), i ' H CH OH HH OHH H OH OH or chemical name: 3-O-[B-D-glucopyranosyl (1->2)]-ax-L-arabinofuranosy (1->3)- -D-glucuronopyranosyl-21,22-0-diangeloyl 10 3B, 15a, 16a, 21B3, 22cc, 24B, 28-heptahydroxyolean-12-ene; d) An isolated, purified or synthesized compound is having structure Xanifolia (Y8), O-C> Y-8 , OH 0 OH COOH OH HO 0 H OHor chemical name: 3-O-[#8-glucopyranosyl 15 (1->2)]-a-arabinofuranosyl (1->3)-,8-glucuronopyranosyl-21, 22-O-diangeloyl-3, 16a, 21,8, 22a, 24,8, 28-hexahydroxyolean-12-ene; e) An isolated, purified or synthesized compound is having structure Xanifolia (Y9), HH HO S OH 20 OH ,or chemical name: 3-O-[p-galactopyranosyl (1->2)]-ao-arabinofuranosyl (1->3)-#8-glucuronopyranosyl-21-0-(3,4-diangeloyl)-a AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 93 rhamnopyranosyl-28-0-acetyl-3#, 16a, 21,#, 22a, 28-pentahydroxyolean-12-ene; and f) An isolated, purified or synthesized compound is having structure Xanifolia 5 (Y10), Y-10 s -9 OH 0 OH O HO O L...oI OH or chemical name: 3-O-[#-galactopyranosyl (1 ->2)]-ca-arabinofuranosyl (1 ->3)--glucuronopyranosyl 21, 22-0-diangeloyl-3p, 16a, 21, 22a, 28-pentahydroxyolean-1 2-ene. 10 g) An isolated, purified or synthesized compound is having structure Xanifolia (YO), H<C ,29 CH CH< <j~~ OO <O27 HO H DH HO OH OH or chemical name: 3-0-[p-D galactopyranosyl(1 ->2)]-c-L-arabinofuranosyl(1 ->3)-p-D-glucuronopyranosyl-21 O-angeloyl, 22-O-(2-methylpropanoyl)-3p, 15cc, 16, 21D, 22, 28 15 hexahydroxyolean-1 2-ene, h) An isolated, purified or synthesized compound is having structure Xanifolia (X), <0 .kH, ""0 -- H .H OHH 0 < 2 7 HO HO HO OH or chemical name: 3-0-{[,-D galactopyranosyl (1-->2)]-[a-L-arabinofuranosyl (1 ->3)]--D-glucuronopyranoside 20 butyl ester}-21-O-acetyl-22-O-angeloyl- 3,6,16a,21,22a,28-pentahydroxyolean 12-ene. i) An isolated, purified or synthesized compound is having structure (Y7), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 94 HO HO HO OHor chemical name: 3-O-[#3-D galactopyranosyl-(1 -*2)]-a-L-arabinofuranosyl-(1 -- 3)-f3-D--glucuronopyranosyl 21-0-angeloyl-28--2-methylbutanoyl-3#3, 15 a, 16a, 218, 22a, 28 hexahydroxyolean-1 2-ene 5 j) An isolated, purified or synthesized compound is having structure (ACH-Y): 0-C OH o H o~r 2 . OH OH HO. k) An isolated, purified or synthesized compound is having structure: 30 29Hj OH C2O O 10 OH or chemica name: 3-O-[p-glucopyranosyl (1 ->2)]- #3-arabinofuranosyl (1 -4)-#6-glucuronopyranosyl 21 -0-angeloyl-22-0-acteyl-3, 1 6cr, 21 3p, 22cr, 241, 28-hexahydroxyolean-12 ene; 15 I) C 2H H 00 HO OY5 AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 95 m) R2 0 OH HO 0 0 COOH R OH O . HC O HO HO CH , OH HO HO OH , wherein R1, R2, are O(C=O)C(CH3)=CH(CH3), R3 is OH, R4 is OH 5 (n) H3C, CH HC H CH3 H3C0 '~OH HC CH "OH CH 3 HO CCH, H 3 C CH ACH-Mb5 (0) H." 3 C 30 2 CH 3 OH 0 C CH CCOH27 HO h OHO O 2 ' 2 7 HO HO OH OH 0 HO OH 1 0 3-0-[f-D-galactopyranosyl(1 ->2)]-3- D-xylopyranosyl (1 ->3)-3-D glucuronopyranosyl-21 -O-angeloyl, 22-O-angeloyl-3 1, 1 5c, 21 J, 22ca, 28 pentahydroxyolean-132-ene, named Ba 1 (p) 25 26 o CHC OHH COOH 27H HO HC C H 0H 0 ~o 0 OH OH Z12, 15 3-0-[D-D-galactopyranosyl(1 -- 2)]-p- D-xylopyranosyl (1 -- 3)-13-D glucuronopyranosyl-21-0-angeloyl, 22-0- tigloyl -3, 16a, 21j, 22a, 28 pentahydroxyolean-1 2-ene; AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 96

24. The method of claim 13, wherein the expression of the following genes is inhibited (represented by gene symbol): AKR1C3, SLC35A3, NEK9, CAV1, USP11, KRT7, TGM2, NCSTN, COG6, 5 WDR4, GPAA1, GUSB, UBAP2L, NMT2, C9orf10, KIAA0251, BTD, EMPI, KRT18, OS9, CPSF1, PSMD1, RNPEP///UBE2V1 /// Kua /// Kua-UEV, NAGA, PARVA, HYOU1, ARMC4, APEH, BTD, FER1 L3, CFH /// CFHL1, COL5A2, EFEMP1, COL18A1, HSDL2, NUP188, IDS, PLOD1, CPM, SPTAN1, LAMP2, ARNTL2, PLOD2, KDELR3, KIAA0586, SMARCA1, PRSS23, PTPRJ, LEPREL1, 10 H2AFV, CAD, URB, CPNE3, DKFZP586J0619, SERPINB7, CNAPI, EEF2K, IKBKAP, SLC25A21, KDELR3, PDIA6, CAV2, COL4A2, MAGED2, PHF19, OACT2, JAG1, FAM62A, KDELR3, PIK4CA, USP5, ZDHHC20, H2AFV, PTPRF, PEG10, P4HA1, MAGED2, PRSS23, PTPRF, CHRDL1, C6orf65, APLP2, EXT2, COPG, SKIV2L, PDIA4, MYH9, SEC31 L1, GANAB, COL5A1, ZNF1 85, DDB1, 15 HDLBP, AP2B1, TSC2, IPO4, FLNA, TLN1, PRKDC, COL6A3, NTNG1, LEPR, RGS4, FN1, GPC6, LEPR, RGS4,IGFBP3; or wherein the expression of the following genes are stimulated (represented by gene symbol): P8, KRTAP4-7, DUSP10, CLDN14, ANGPT2, DUSP10, GDF15, GPNMB, HDAC9, HECW2, C14orf78, UPP1, PPP1R15A, PLEKHM1, STX3A, ANGPT2, 20 SQSTM1, RHOQ, STC2, PPP1R15A, LOC286044, ATF3, HMOX1, CXCL2, CD33L3, LRRC8E, SESN2, LIF, TFP12, KIAA11706, RRAGC, DDIT3, DYRK3, CTNS, GPNMB, CEBPB, CCL20, AMIGO2, KIAA1462, HSPBAP1, EVC, CLN8, ABL2, SGEF, MCTP1, IRS2, C14orf109, TNFAIP3, RND3, ZFHX1B, LHFPL2, SNF1LK, SLC3A2, NAV2, SPOCD1, TFP12, EV12A, ST3GAL6, CSTB, ROBO4, 25 GNPDA1, GEM, IRS2, HMGA2, PALM2-AKAP2, BR13, KIAA1754, VDR, NEU1, INSIG1, C17orf32, ABL2, PALM2-AKAP2, MTERFD3, ZNF697, NFKBIZ, BCL6, THRAP1, MGC5618, ADAMTS1, MAFG, NPC2, CITED2, TRIB3, ZCCHC9, RNU17D, CITED2, RRS1, NSUN5C, PBX2, RG9MTD1, SGSH, INSIG1, MGC16291, RAB9A, ARMCX6, SERPINB2, ATP6V1B2, DKFZP56411171, 30 ATP6VOE, HSPC196, MRPS30, ARMCX1, LOC339229, ANKRD11, C9orf103, PSEN2, ADAMTS1, SNAPC1, RNF25, ZNF278, TGFBI, UAP1 L1, PDE4DIP, MGC1 9764, TMEM60, CEP4, KIAA1 211, DDX20, CSRP2BP, ZNF690, TRIO, CLTA, ATP6VOE, RAB32, MRPS31, LOC90693, ATP6V1 C1, CBLL1, YTHDF2, FLJ14466, ARL10C, BCL2A1; or wherein the expression of the following genes 35 are stimulated (represented by gene symbol): CXCL2, CSF2, 1L6, NFKBIZ, CXCL3, EGRI, CLDN14, ATF3, IL1A, CSF3, PTGS2, NFKBIZ, KRTAP4-9, TNFAIP3, ABL2, KRTAP4-7, MMP3, DUSP1O, FOS, DUSP1, PPP1R15A, AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 97 DDIT3, DUSP10, HECW2, DSCR1, SESN2, TSLP, SLC7A11, HES1, SESN2, CXCL1, TAGLN3, HBEGF, IER3, RAB2, P8, 1L8, GADD45A, LOC441461, GEM, LIF, KLF6, MGC4504, CCL20, PRB1 /// PRB2, THRA /// NR1 Dl, ERN1, NECAP2, DKK3, GNAO1, NFKBIA, CREB5, CLDN1, CDKN1A, PRDM1, 5 SERPINB2, CD274, FST, LOC401317, BIRC3, PMAIP1, BMP2, 1L24, BMP2, WHDC1L2, SGK, RND3, UPP1, C14orf34, ARID1B, KLF6, KLHL24, MAFF, IL1 2A, SAT, NSD1, JUNB, DUSP1, SLC3A2, ASNS, MAFF, PSAT1, CLTA, ZC3H12C, CLDN1, IL1B, ROBO4, RARA, BCL6, SLC7A11, PDE4DIP, ZNF697, ATP2A2, ZFP36, REST, HDAC9, STAC2, LOC153222, ZC3H12A, SLC25A37, 10 1L17C, TRIB3, CEBPB, PTX3, TRIB3, KIAA1718, ZNF385, TTMP, MGC5618, CSF2, DUSP5, SLC25A25, ADAMTS1, TFRC, SEC15L2, SCNN1A, HES1, LOC153222, C20orf72, ETS1, GDF15, KIAA1754, PACRG, PRSS22, TFRC, AQP2, STX3A, REM1, LIMK2, STC2, ISG20L1, BCL2A1, HES4, TJP3, SLC7A5, CEBPG, LILRB2 /// LILRB3, LOC389429, LLGL1, KLF6, CSNK1E, DUSP1, 15 ICAM1, PYY2, TPCN1, MFSD2, KIAA0690, SOD2, E2F7, GRIK5, PAD11, HIP1R, IRAK2, EIF1, CEBPG, GOS2, KIAA0690, NEDD4L, MXD1, TXNDC5, PERLD1, HIFlA, RDH13, CTH, ETS2, FAH, CLK4, RIMS4, FLJ12355, LDLR, WARS, IFRD1, LRCH4, SLC1A4, FST, PPIF, ARHGEF2, PMAIP1, PBEF1, Cl4orf159, ATF4, FLJ90119, TGFBR3, DDX21, MUC8, TNFSF7, SPTLC2, 20 KBTBD8, CIAS1, KIAA0476, NFKB1, DES /// FAM48A, ICAM1, INHBA, MARS, Clorf1 13, GRK6, TCF2, SLC7A1, TNFRSF1OB, IER2, TFRC, SOS2, CARS, HAB1 /// LOC442496, KLHL24, SQSTM1, GIT1, IRS2, SARS, TRIM25, JUN, YRDC, ETS1, CTH, ABL2, CD274, FZD8, EREG, PFDN2, TMEM63B, DYRK3, GARS, RASSF8, CAMTA2, HOXC8, AARS, TBX3, RRAGC, BCAP29, 25 TNFRSF10B, MCL1, PALM2-AKAP2, TMEM22, ZNF548, PCBP2, SLC1A4, FSTL3, TA-PP2C, PIM3, MAFG, NOL1, PEA15, ETS2, IQCG, BEX2, C12orf39, LDLR, VEGF, CCNL1, LOC440069, SNAPC1, SLC27A5, MARS, ICAM1, AXUD1, KCNIP2, LOC146177 /// FLJ40941, GOT1, C11orf17 /// NUAK2, TTBK1, SNCA, NFRKB, GRB2, ADAMTS1, PALM2-AKAP2, CCNL1, JUN, SPRY4, 30 SLC38A1, E2F7, MGC27165, IDS, SLC7A1, FLJ11021, KCNK5, GYPC, MYC, CACNG6, PHLDA1, INSIG1, FLJ13448, LOC202051, GALNT10, TFEB, ABL2, MTHFD2, SERPINB8,TNPO2, MCF2L, SERTAD1, SPRY2, PHLDA1, SLC7A11, CXCL5, COMT, GTPBP2, RAB4B, ATXN7, OTUD5, VEGF, ADAMTS6, YARS, NAV3, SAMD4, C17orf32, SHMT2, CHIC2, ORAOV1, CREM, ALS2CL, 35 AMIGO2, MGC19764, SFPQ, MGC11257, PLEKHM1, MMP28, SLC4A5, DNAJB9, ERRF11, FZD8, MGC4399, GUCA1B, ATP13A3, KIAA0020, XBP1, ATP6V1B2, IGLV3-25, CHD4, GRB10, FLJ40089, CLDN19, NPC1, RIPK2, AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 98 PLEKHF2, LOC283314, RSPO3, GSK3A, ANKRD11, WARS, GNPDA1, IGKC/// IGKV1-5, RCL1, C9orf91, TIMM10, SLC1A4, ODC1, SLC38A1, EIF4EBP1, ZNF267, YRDC, CHD4, PER1, NFKBIE, INSIG1, FLJ11259, NCOA3, TNPO2, BAZ2A, SLC1A5, KRTAP2-1, PDE4DIP, EPB41L3, CITED2, JTV1, TA-PP2C, 5 METRNL, BCL10, Clorf19, PTP4A1, PDE4DIP, CPSF1, TIMM10, IGSF21, TM4SF1, CDK6, BANP, PHLDA1, PAPPA2, MGC17337, TNFRSF19L, ADAMTS10, CBFB, HERPUD1, RTTN, FLJ13855, SYNPO, NAV2, FLJ34208, DDX10, C6orf66, LOC56902, CHMP1B, HIPK2, H3F3B, NAV3, ELL2, NSUN5C, PLAUR, UCK2, PBEF1, TP53BP2, TEX10, B3GNT5, USP36, INHBA, SPIRE1, 10 CSTB, NSUN5C, TFPI2; or wherein the expression of the following genes is inhibited: FN1, ITGAV, LAMA4, LAMB2, LAMC1, LAMB1, LAMB1, LAMA4, LAMA5, LAMC1, LAMA2, LAMB1, LAMA3, SCAMPI, TICAM2, SCAMPI, TICAM2, SCAMPI, SCAMPI, CAMK 2B, DL1, ICAM3,CEECAM1,ICAM5,SCAMP1, CAMK1G, CAMSAP1, MCAM, CAMTA1, 15 CKN1, ALCAM, DCAMKL2, CEACAM3, CAMK2D, CAMK2B, SCAMP5, CAMK4, NCAM1, CAMK2G, MYH9, MYH10, MYO1D, MYO5A, MYLK, MYO6, MYO5A, MYO1C, MYLK, MYO6, MYLC2PL, MYO10, MYO6, TPM3, MYO1C, BECN1, MYO1E, TPM3, M-RIP, MYO1B, MYO10, MYO5A, M-RIP, MYO10, MYL6, MYOHD1, BECN1, TPM4, MYLK, MYH10, MYOHD1, LOC221875, LOC402643, 20 MYO15B, LOC129285, MYH11, MYO1B, MYO1C, MYO9B, CDH13, CTNNAL1, CDH13, CDH12, CTNNB1, CDH5, CTNND1, CDH2, CTNNA1, CDH2, PCDHB16, CTNNA1, CELSR2, PCDHB6, PCDHB7, CTNND2, PCDHGC3, PCDHGB4, PCDHGA8, PCDHGA12, PCDHGC5, PCDHGC4, PCDHGB7, PCDHGB6, PCDHGB5, PCDHGB3, PCDHGB2, PCDHGB1, PCDHGA11, 25 PCDHGA10, PCDHGA9, PCDHGA7, PCDHGA6, PCDHGA5, PCDHGA4, PCDHGA3, PCDHGA2, PCDHGA1, CTNND1, CDH23, PCDHB12, PCDHB10, PCDH18, CDH20, PCDH9, PCDHGA12, PCDHGA11, PCDHGA10, PCDHGA6, PCDHGA5, PCDHGA3, PCDH7, CDH18, CDH6, CCBE1, CO10A1, COL12A1, COL13A1, COL18A1, COL1Al, COL21A1, COL4A1, COL4A2, COL4A5, 30 COL4A6, COL5A1, COL5A2, COL6A1, COL6A2, COL6A3, COL9A1, MMP9, P4HA1, P4HA2, P4HB, PCOLCE, PCOLCE2, PCOTH, PLOD1, PLOD2, PLOD3, CIB1, ILK, ITGA2, ITGA3, ITGA4, ITGA6, ITGAV, ITGB1, ITGB1BP1, ITGB2, ITGB5, ITGBL1, TNC, EMILIN1, ICAM1, HSPG2, HPSE, HS2ST1,SDC2, AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 99

25. A pharmaceutical composition for modulating the secretion or expression of adhesion protein of cells, modulating the gene expression, modulating the secretion or expression of angiopoietin, enhancing an immune response, providing adjuvant activities, providing vaccine activities, or inhibiting the 5 metastasis of cancer cell in a subject, wherein the composition comprises a compound or its salt or ester thereof as an effective component selected from the formula: R, R 14 Ri R 16 R 4 R 11 R 12 R2 13RR R 3 R, R 10 , also named (1 E), wherein R1 is selected from hydrogen, hydroxyl, 0-angeloyl, O-tigloyl, O-senecioyl, 0 10 alkyl, 0-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, O-aryl, 0-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; R2 is selected from hydrogen, hydroxyl, 0-angeloyl, 0-tigloyl, O-senecioyl, 0 alkyl, 0-dibenzoyl, O-benzoyl, 0-alkanoyl, O-alkenoyl, O-benzoyl alkyl 15 substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, 0-acyl, 0-heterocylic, O-heteroraryl, and derivatives thereof; R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-alkyl, 0-dibenzoyl, O-benzoyl, 0 alkanoyl, 0-alkenoyl, 0-benzoyl alkyl substituted 0-alkanoyl, 0-alkanoyl 20 substituted phenyl, 0-alkenoyl substituted phenyl, O-aryl, 0-acyl, 0-heterocylic, O-heteroraryl, and derivatives thereof; R3 is H or OH; R8 is H or OH, preferably OH; R1 6 is H ,or R4 and R1 6 may form an oxygen bridge with divalent radical formula of -CH2-0-, CH(OH)-O- or C(=0)-O-, wherein the -0- may be replaced with 25 NH- ; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; R5 is a hydrogen, heterocyclic or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, 30 mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; wherein R9, R10, R11, R12, R13, R14, R15 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 100 heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, CH 2 0- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, R2 and R6 are compriseing a group selected from O-angeloyl, O-tigloyl, 0 senecioyl, 0-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl 5 substituted O-alkanoyl, O-aryl, O-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; 10 or wherein R4 is CH 2 R6, wherein R1 and R2 independently consists an 0 angeloyl group, or at least two of R1, R2 and R6 are 0-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two 0-angeloyls; or wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, 15 dose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises glucuronic acid, arabinose and galactose; or wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, 20 galacturonic acid, and a derivative or combination thereof; or wherein R5 is 3-p O-{[(ca-L-rhamnopyranosyl-(1 ->2)]-ax-L-rhamnopyranosyl--(1 ->2)--D galactopyranosyl--(1 ->3)]-[p-D- galactopyranosyl--(1 ->2)]- p-D glucuronopyranosyl} 25 26. The pharmaceutical composition of claim 25, wherein at least one of R1 and R2 of the compound is selected from O-acetyl, O-angeloyl, O-tigloyl, O-senecioyl, 0 dibenzoyl, and O-benzoyl, or at least one of R1 and R2 is a sugar moiety substituted with two groups selecting from acetyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl; R5 is a hydrogen or sugar moiety(ies), wherein the sugar 30 moiety(ies) is/are selected from a group of glucose, galactose, arabinose and derivatives thereof, wherein the derivatives are acid, ester and salt.

27. The pharmaceutical composition of claim 25, wherein the modulating secretion or expression of adhesion of cancer cell comprises inhibiting the secretion or 35 expression of adhesion protein, wherein the adhesion proteins comprise fibronectin, integrins family, Myosin, vitronectin, collagen, laminin, polyglycans, cadherin, heparin, tenascin, CD 54 and CAM; wherein the inhibiting protein AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 101 expressed from genes, including ITGAV, TNC, COLlAl, FN1, LAMA4, family protein relate to potassium channel, RAB3B, thrombospondin, insulin-like growth factor, G-protein and Glypican. 5 28. The pharmaceutical composition of claim 25, wherein the modulating the secretion or expression of adhesion protein comprises reducing the secretion or expression of fibronectin for inhibiting the metastasis or growth of cancer cells, wherein the cancer is selected from breast, leukocyte, liver, ovarian, bladder, prostate, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervix, 10 esophagus, testis, spleen, kidney, lymph, pancreas, stomach and thyroid cancer.

29. The pharmaceutical composition of claim 25, wherein the modulating secretion or expression of angiopoietin comprising angiopoietin 1, angiopoietin 2, angiopoietin 3, angiopoietin 4, angiopoietin 5, angiopoietin 6 and angiopoietin 7; or wherein 15 the angiopoietin is comprising angiopoietin-like 1, angiopoietin-like 2, angiopoietin -like 3, angiopoietin-like 4, angiopoietin-like 5, angiopoietin-like 6 and angiopoietin-like 7; or wherein the modulating secretion or expression of angiopoietin comprises positive and negative regulating; wherein modulating angiopoietin comprises stimulating secretion or expression of the angiopoietin 2 20 in order to inhibit angiogenesis; or wherein modulating angiopoietin comprises inhibiting secretion or expression of the angiopoietin 1 in order to inhibit angiogenesis; or wherein modulating angiopoietin comprises inhibiting secretion or expression of the angiopoietin-like 1; or wherein modulating angiopoietin comprises inhibiting the secretion or expression of angiopoietin-like 4. 25

30. The pharmaceutical composition of claim 25, wherein the modulating gene expression includes increasing the expression of the protein phosphatase 1, dual specificity phosphatase 10; or increasing expression of the genes of ANGPT2, DDIT3, LIF and NFKB1Z. 30 AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 102

31. The pharmaceutical composition of claim 25, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound is having structure Xanifolia(Y), Y 3 I0 OH 0 HO H H HOH OH or chemical name: 3-0-[P-D 5 galactopyranosyl (1 ->2)]-a-L-arabinofuranosy (1 ->3)-B-D-glucuronopyranosyl 21,22-O-diangeloyl-3B, 15cx, 16a, 21 B, 22ax, 28-hexahydroxyolean-1 2-ene; b) An isolated, purified or synthesized compound is having structure Xanifolia (Y1), OAc OH SOH H H H O OH 10 OH or chemical name: 3-O-[B-D-galactopyranosyl (1 ->2)]-a-L-arabinofuranosyl (1 ->3)- -D-glucuronopyranosyl-21-0-(3,4 diangeloyl)-ax-L-rhamnophyranosyl-22-O-acetyl-3 ,1 6ax, 21 P, 22x, 28 pentahydroxyolean-1 2-ene; 15 c) An isolated, purified or synthesized compound is having structure Xanifolia (Y2), Y 2 OH 0 O OH OH OO OH 0 OH or chemical name: 3-0-[P-D-glucopyranosyl (1 ->2)]-a-L-arabinofuranosy (1 ->3)- -D-glucuronopyranosyl-21,22-0-diangeloyl 3B, 15cx, 16a, 21BP, 22x, 24P, 28-heptahydroxyolean-12-ene; 20 d) An isolated, purified or synthesized compound is having structure Xanifolia (Y8), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 103 O-c 0 Y-8 '' OH 0 'OH HO OH OH HO OH OH OH or chemical name: 3-0-[-glucopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-p-glucuronopyranosyl-21, 22-O-diangeloyl-3p 16a, 21p6, 22a, 246, 28-hexahydroxyolean-1 2-ene; 5 e) An isolated, purified or synthesized compound is having structure Xanifolia (Y9), -0 Y 9 ""OH OAc "OH HO C HO I' H0 OH 0 0 H H 0 OH0 OH or chemical name: 3-0-[# galactopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-,6-glucuronopyranosyl-21-0 (3,4-diangeloyl)- a-rhamnopyranosyl-28- 0-acetyl-3,#, 16 a, 21 , 22a, 28 10 pentahydroxyolean-1 2-ene; and f) An isolated, purified or synthesized compound is having structure Xanifolia (Y10), -'O-C Y-10 " -/O-e,-- OHOH HO ''*OH HOH H OH , or chemical name: 15 3-0-[p-galactopyranosyl (1->2)]-a-arabinofuranosyl (1->3)-f-glucuronopyranosyl 21, 22-O-diangeloyl-3p, 16a, 21 , 22a, 28-pentahydroxyolean-1 2-ene. g) An isolated, purified or synthesized compound is having structure Xanifolia (YO), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 104 302 2 CH HO HO HO OH , or chemical name: 3-0-[p-D galactopyranosyl(1 ->2)]-ac-L-arabinofuranosyl(1 -*3)-j3-D-glucuronopyranosyl-21 0-angeloyl, 22-0-(2-methylpropanoyl)-3 j, 15ac, 16ca, 21 [, 22ac, 28 hexahydroxyolean-1 2-ene, 5 h) An isolated, purified or synthesized compound is having structure Xanifolia (X), 25 2 c H HQ- 0 23 27 HO HO HO H OH or chemical name: 3-0-{[p-D galactopyranosyl (1 ->2)]-[a-L-arabinofuranosyl (1 ->3)]- -D-glucuronopyranoside butyl ester}-21-O-acetyl-22-O- angeloyl- 3p,1 6a,21,22a,28-pentahydroxyolean 10 12-ene. i) An isolated, purified or synthesized compound is having structure (Y7), H OOH OO 2 2 HON HT HO OH ,or mchlnaemia n(ae 3O[#D galactopyranosyl-(1 -- 2)]-[a-L-arabinofuranosyl-(1--3)-0-D-glucuronopyranosyl 15ty 2--elyl-2-0-2-ethylbut0aneoyl- 3,615 a, 16a,2 2,2a, 28- ethdrxola h012eayrxyla-1-n i) ~ ~ AMNE SHEE (ARTICLE, 19)ido ynhszdcmoudi aigstutrY) WO 2009/117196 PCT/US2009/034115 105 j) An isolated, purified or synthesized compound is having structure (ACH-Y): O-C 0 OH 0 "OH OH HO 5 k) An isolated, purified or synthesized compound is having structure: o 30 "29 H HH 25 26 CHOH 0 COOH 2 7 23 CH2OH H oH 0 0 OH OH O DH 0 O OH OH OH or chemical name: 3-O-[pi-glucopyranosyl (1 ->2)]- p-arabinofuranosyl (1 ->4)-p6- glucuronopyranosyl -21-0-angeloyl-22-0-acteyl-3p8, 16a, 216, 22a, 24p6, 28-hexahydroxyolean-12 ene; 10 (I) An isolated, purified or synthesized compound is having structure: 0H2 H CC H Co 7 O HOH HO OH Y5 (m) An isolated, purified or synthesized compound is having structure: ~RR 0 OH HO O 0 COOH - 2 OH 00 HO O 0HO HOO HD H HO OH HO OH 15 wherein R1, R2, are O(C=O)C(CH3)=CH(CH3), R3 is OH, R4 is OH (n) An isolated, purified or synthesized compound is having structure: AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 106 H3 HHC CH3 H 3 C, H 3 CH~ ~C OH 0 0 3 H 3 OH CH 3 HO H3C CH 3 ACH-Mb5 (o) An isolated, purified or synthesized compound is having structure: RK, R, 7 CH R, R, OH 0RR OH 00 0 HO HO 0 O H HO H ,Wherein R1 is O(C=O)C(CH3)=CH(CH3), R2 5 is O(C=O)CH=CH-C6H5, R3, R4 are OH, R6, R7, R8, R9, R10, R11, R12 are CH3, R13 is COOCH3, also named Mbl2 (p) An isolated, purified or synthesized compound is having structure: S 29 CH co 0 20H CH, OOH OH-H 27 H O 24 23 OH OH 3-0-[-D-galactopyranosyl (1 ->2)]-p- D-xylopyranosyl (1 ->3)-p-D 10 glucuronopyranosyl-21 -0-angeloyl, 22-0-angeloyl-3p, 15a, 21 P, 22a, 28 pentahydroxyolean-1 2-ene, named Ba 1; HO OHO OH Z12, 3-0-[j-D-galactopyranosyl(1 ->2)]-p- D-xylopyranosyl (1 ->3)-p-D glucuronopyranosyl-21-0-angeloyl, 22-0- tigloyl -3s, 16a, 21sP, 22a, 28 15 pentahydroxyolean-1 2-ene; AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 107

32. A pharmaceutical composition for treating parasites in a subject, wherein the composition comprises a compound or its salt or ester thereof as an effective component selected from the formula: R, R 14 R 16 R 4 R 11 R 12 R2 13R, R 5 0 g. R 3 5 R 9 R10 , also named (1 E), wherein R1 is selected from hydrogen, hydroxyl, 0-angeloyl, 0-tigloyl, O-senecioyl, 0 alkyl, 0-dibenzoyl, 0-benzoyl, 0-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, 0-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; 10 R2 is selected from hydrogen, hydroxyl, 0-angeloyl, 0-tigloyl, O-senecioyl, 0 alkyl, 0-dibenzoyl, 0-benzoyl, 0-alkanoyl, O-alkenoyl, 0-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, 0-aryl, 0-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from 15 hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, 0-alkyl, 0-dibenzoyl, O-benzoyl, 0 alkanoyl, O-alkenoyl, 0-benzoyl alkyl substituted 0-alkanoyl, 0-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, O-aryl, O-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; R3 is H or OH; R8 is H or OH, preferably OH; 20 R1 6 is H ,or R4 and R1 6 may form an oxygen bridge with divalent radical formula of -CH2-0-, CH(OH)-O- or C(=O)-0-, wherein the -0- may be replaced with N- ; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; wherein the sugar moieties can not be 5, if the oxygen bridge is formed between R4 and R16; R5 is a hydrogen, heterocyclic or sugar 25 moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combination thereof; wherein R9, R10, R11, R12, R13, R14, R15 are 30 independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO alkyl, COO-aryl, COO-heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0 heterocyclic, CH 2 0- heteroaryl, alkyls group, hydroxyl, acetyl group, particularly CH 3 ; wherein at least two of R1, R2 and R6 are compriseing a group selected AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 108 from O-angeloyl, O-tigloyl, O-senecioyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, 0 alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-aryl, O-acyl, 0-heterocylic, 0-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety substituted with at least two groups selected from a group 5 consisting of angeloyl, acetyl, tigloyl, senecioyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and a derivative thereof; or wherein R4 is CH 2 R6; wherein R1 and R2 independently consists an 0-angeloyl group, or at least two of R1, R2 and R6 are 0-angeloyl or at least one of R1, R2 or R6 is a sugar moiety with two 0 10 angeloyls; or wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronis acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, or the combination thereof; wherein the sugar preferably comprises 15 glucuronic acid, arabinose and galactose; or wherein R5 is/are sugar moiety(ies) selected from a group consisting of glucose, galactose, arabinose, alduronic acid, glucuronic acid, galacturonic acid, and a derivative or combination thereof; or wherein R5 is 3-j-0-{[(a-L-rhamnopyranosyl-(1->2)]-a-L-rhamnopyranosyl- (1->2)-P-D- galactopyranosyl--(1->3)]-[P-D- galactopyranosyl--(1 ->2)]- P-D 20 glucuronopyranosyl}

33. The pharmaceutical composition of claim 32, wherein at least one of R1 and R2 is selected from O-acetyl, 0-angeloyl, 0-tigloyl, 0-senecioyl, 0-dibenzoyl, and 0 benzoyl, 0-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl, or at least 25 one of R1 and R2 is a sugar moiety substituted with two groups selecting from acetyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl 0-alkanoyl substituted phenyl, 0-alkenoyl substituted phenyl; R5 is a hydrogen or sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, arabinose and derivatives thereof, wherein the derivatives are acid, 30 ester and salt.

34. The pharmaceutical composition of claim 32, wherein the antiparasitics comprise inhibiting leishmaniases, amoebiasis, trypanosomiasis, toxoplasmosis or malaria. AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 109

35. The pharmaceutical composition of claim 32, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound is having structure Xanifolia(Y), Y3 0 OH OHH H OHOH H OH or chemical name: 3-0-[P-D-galactopyranosyl 5 (1 -2)]-a-L-arabinofuranosy (1 -3)-5-D-glucuronopyranosyl-21,22-O-diangeloyl 3@, 15cx, 16a, 21 @, 22cx, 28-hexahydroxyolean-1 2-ene; b) An isolated, purified or synthesized compound is having structure Xanifolia (Y1), Y 1 OH '0 H OH 10 or chemical name: 3-0-[P-D-galactopyranosyl (1 ->2)]-a-L-arabinofuranosyl (1 ->3)- -D-glucuronopyranosyl-21-0-(3,4 diangeloyl)-a-L-rhamnophyranosyl-22-O-acetyl-3 ,1 6ax, 21 P, 22x, 28 pentahydroxyolean-1 2-ene; 15 c) An isolated, purified or synthesized compound is having structure Xanifolia (Y2), Y2 H HO OHH H H O HOH or chemical name: 3-0-[P-D-glucopyranosyl (1 -2)]-a-L-arabinofuranosy (1 -3)- -D-glucuronopyranosyl-21,22-O-diangeloyl 3P, 15ax, 16ax, 21 P, 22ax, 24P, 28-heptahydroxyolean-12-ene; 20 d) An isolated, purified or synthesized compound is having structure Xanifolia (Y8), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 110 Y-8 OH 0 "OH HO 0 OH HO 0 OH OH or chemical name: 3-O-[3-glucopyranosyl (1 -- 2)]-a-arabinofuranosyl (1 -- 3)-p8-glucuronopyranosyl-21, 22-O-diangeloyl-3, 16a, 21p6, 22a, 24p8, 28-hexahydroxyolean-12-ene; 5 e) An isolated, purified or synthesized compound is having structure Xanifolia (Y9), Y9 "OH OAc O ' HO O .. , - O O HO O HOH ,or chemical name: 3- 0-[p-galactopyranosyl (1->2)]-amarabinofuranosyl (1->3)-p6-glucuronopyranosyl-21-O-(3,4-diangeloyl)-a rhamnopyranosyl-28-0-acetyl-3p8, 16a, 21p, 22a, 28-pentahydroxyolean-12-ene; 10 and f) An isolated, purified or synthesized compound is having structure Xanifolia (Y1 0), 0, Y-10 "'O O H C HC H OH I -0 O HO 0 OH OH ,or chemical name: 15 3-0-[p-galactopyfuranosy (1-a(13)-p-glucuronopyranosyl 21, 22-O-diangeloyl-3p, 16a1, 1 22a, 28-pentahydroxyolean-1 2-ene. g) An isolated, purified or synthesized compound is having structure Xanifolia (YO), AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 111 25 22H 0 00020 2 O2 COOH DH HO- H o HHOO OH OH or chemical name: 3-O-[p-D galactopyranosyl(1 ->2)]-c-L-arabinofuranosyl(1 ->3)-p-D-glucuronopyranosyl-21 O-angeloyl, 22-0-(2-methylpropanoyl)-3p, 15ca, 16a, 21 P, 22a, 28 hexahydroxyolean-1 2-ene, 5 h) An isolated, purified or synthesized compound is having structure Xanifolia (X), l5H0 o -2 2 7 O O 2 '2 HO HO HO OH or chemical name: 3-0-{[#8-D galactopyranosyl (1->2)]-[a-L-arabinofuranosyl (1->3)]--D-glucuronopyranoside butyl ester}-21-0-acetyl-22-0-angeloyl- 3#,16a,21#8,22a,28-pentahydroxyolean 10 12-ene. i) An isolated, purified or synthesized compound is having structure (Y7), HI -~ 0 0222 25 2 o o. 27 OH O 2 2 HO HOH HO 22 0 OH OH or chemical name: 3-O-[jG-D galactopyranosyl-(1 -- 2)]-a-L-arabinofuranosyl-(1 ->3)-0-D--glucuronopyranosyl 15 21-0-angeloyl-28-0-2-methylbutanoyl-3#, 15 a, 16a, 21#, 22a, 28 hexahydroxyolean-1 2-ene j) An isolated, purified or synthesized compound is having structure (ACH-Y): 20 O-C OH 0 OH HO AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 112 k) An isolated, purified or synthesized compound is having structure: DH, C 2O 27 2 2 CHO2 0 C H OO 4HO OHOH 0 0 H0 NO OH 0~O OH OH or chemical name: 3-0-[,-glucopyranosyl (1 -*2)]- -arabinofuranosyl (1 -4)-6-glucuronopyranosyl 21 -O-angeloyl-22-0-acteyl-3,#, 16a, 216, 22a, 24#6, 28-hexahydroxyolean-12 5 ene; I) c 0 90 C H3 D H OH HQ24 23 HO OH 0 OH OH Y5 10 m) HO HO Q OH 7 OH HO OH 0 o 000H "4 o H 00 HO H 00OH HO HOH HO OH HO OH wherein R1, R2, are O(C=O)C(CH3)=CH(CH3), R3 is OH, R4 is OH (n) H3C OH3 0 . , H C CH3 H3C CH, ""OH 0 CH 3 HO. 15 H3C 'CH3 ACH-Mb5 AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 113 (o) 3 23 HC 4 5 26 CH 3 CF o CF 3 OH COOH 27 HO O H OH 0 OH 3-0-[B-D-galactopyranosyl (1 ->2)]-p- D-xylopyranosyl (1 ->3)-s-D glucuronopyranosyl-21-0-angeloyl, 22-0-angeloyl-3p, 15c, 21 P, 22ca, 28 5 pentahydroxyolean-1 2-ene, named Ba 1; (p) H H OH HO OH 1 C< 27 0<3 CH Z12, 3-O-[P-D-galactopyranosyl(1 ->2)]-p- D-xylopyranosyl (1 ->3)-p-D glucuronopyranosyl-21-0-angeloyl, 22-0- tigloyl -3B, 16a, 21$, 22a, 28 10 pentahydroxyolean-1 2-ene;

36. The pharmaceutical composition of claim 25, wherein the expression of the following genes is inhibited (represented by gene symbol): AKR1C3, SLC35A3, NEK9, CAVI, USP11, KRT7, TGM2, NCSTN, COG6, 15 WDR4, GPAA1, GUSB, UBAP2L, NMT2, C9orf1O, KIAA0251, BTD, EMPI, KRT18, OS9, CPSF1, PSMD1, RNPEP///UBE2V1 /// Kua/// Kua-UEV, NAGA, PARVA, HYOU1, ARMC4, APEH, BTD, FER1 L3, CFH /// CFHL1, COL5A2, EFEMP1, COL18A1, HSDL2, NUP188, IDS, PLODI, CPM, SPTAN1, LAMP2, ARNTL2, PLOD2, KDELR3, KIAA0586, SMARCA1, PRSS23, PTPRJ, LEPREL1, 20 H2AFV, CAD, URB, CPNE3, DKFZP586JO619, SERPINB7, CNAP1, EEF2K, IKBKAP, SLC25A21, KDELR3, PDIA6, CAV2, COL4A2, MAGED2, PHF19, OACT2, JAG1, FAM62A, KDELR3, PIK4CA, USP5, ZDHHC20, H2AFV, PTPRF, PEG10, P4HA1, MAGED2, PRSS23, PTPRF, CHRDL1, C6orf65, APLP2, EXT2, COPG, SKIV2L, PDIA4, MYH9, SEC31 L1, GANAB, COL5A1, ZNF1 85, DDB1, 25 HDLBP, AP2B1, TSC2, IP04, FLNA, TLN1, PRKDC, COL6A3, NTNG1, LEPR, RGS4, FN1, GPC6, LEPR, RGS4,IGFBP3; or wherein the expression of the following genes are stimulated (represented by gene symbol): AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 114 P8, KRTAP4-7, DUSP10, CLDN14, ANGPT2, DUSP10, GDF15, GPNMB, HDAC9, HECW2, C14orf78, UPP1, PPP1R15A, PLEKHM1, STX3A, ANGPT2, SQSTM1, RHOQ, STC2, PPP1R15A, LOC286044, ATF3, HMOX1, CXCL2, CD33L3, LRRC8E, SESN2, LIF, TFP12, KIAA1706, RRAGC, DDIT3, DYRK3, 5 CTNS, GPNMB, CEBPB, CCL20, AMIGO2, KIAA1462, HSPBAP1, EVC, CLN8, ABL2, SGEF, MCTP1, IRS2, C14orf109, TNFAIP3, RND3, ZFHX1B, LHFPL2, SNF1 LK, SLC3A2, NAV2, SPOCD1, TFP12, EV12A, ST3GAL6, CSTB, ROBO4, GNPDA1, GEM, IRS2, HMGA2, PALM2-AKAP2, BR13, KIAA1754, VDR, NEU1, INSIGI, C17orf32, ABL2, PALM2-AKAP2, MTERFD3, ZNF697, NFKBIZ, BCL6, 10 THRAP1, MGC5618, ADAMTS1, MAFG, NPC2, CITED2, TRIB3, ZCCHC9, RNU17D, CITED2, RRS1, NSUN5C, PBX2, RG9MTD1, SGSH, INSIGI, MGC16291, RAB9A, ARMCX6, SERPINB2, ATP6V1B2, DKFZP56411171, ATP6VOE, HSPC196, MRPS30, ARMCX1, LOC339229, ANKRD11, C9orf103, PSEN2, ADAMTS1, SNAPC1, RNF25, ZNF278, TGFBI, UAP1 L1, PDE4DIP, 15 MGC1 9764, TMEM60, CEP4, KIAA1 211, DDX20, CSRP2BP, ZNF690, TRIO, CLTA, ATP6VOE, RAB32, MRPS31, LOC90693, ATP6V1C1, CBLL1, YTHDF2, FLJ14466, ARL10C, BCL2A1; or wherein the expression of the following genes are stimulated (represented by gene symbol): CXCL2, CSF2, 1L6, NFKBIZ, CXCL3, EGR1, CLDN14, ATF3, IL1A, CSF3, PTGS2, NFKBIZ, KRTAP4-9, 20 TNFAIP3, ABL2, KRTAP4-7, MMP3, DUSP10, FOS, DUSP1, PPP1R15A, DDIT3, DUSP10, HECW2, DSCR1, SESN2, TSLP, SLC7A11, HES1, SESN2, CXCL1, TAGLN3, HBEGF, IER3, RAB2, P8, 1L8, GADD45A, LOC441461, GEM, LIF, KLF6, MGC4504, CCL20, PRB1 /// PRB2, THRA /// NR1 D1, ERN1, NECAP2, DKK3, GNAO1, NFKBIA, CREB5, CLDN1, CDKN1A, PRDM1, 25 SERPINB2, CD274, FST, LOC401317, BIRC3, PMAIP1, BMP2, 1L24, BMP2, WHDC1L2, SGK, RND3, UPP1, C14orf34, ARID1B, KLF6, KLHL24, MAFF, IL1 2A, SAT, NSD1, JUNB, DUSP1, SLC3A2, ASNS, MAFF, PSAT1, CLTA, ZC3H12C, CLDN1, IL1B, ROBO4, RARA, BCL6, SLC7A11, PDE4DIP, ZNF697, ATP2A2, ZFP36, REST, HDAC9, STAC2, LOC153222, ZC3H12A, SLC25A37, 30 IL17C, TRIB3, CEBPB, PTX3, TRIB3, KIAA1718, ZNF385, TTMP, MGC5618, CSF2, DUSP5, SLC25A25, ADAMTS1, TFRC, SEC15L2, SCNN1A, HES1, LOC-153222, C20orf72, ETS1, GDF15, KIAA1754, PACRG, PRSS22, TFRC, AQP2, STX3A, REM1, LIMK2, STC2, ISG20L1, BCL2A1, HES4, TJP3, SLC7A5, CEBPG, LILRB2 /// LILRB3, LOC389429, LLGL1, KLF6, CSNK1E, DUSP1, 35 ICAM1, PYY2, TPCN1, MFSD2, KIAA0690, SOD2, E2F7, GRIK5, PAD11, HIP1R, IRAK2, EIF1, CEBPG, GOS2, KIAA0690, NEDD4L, MXD1, TXNDC5, PERLD1, HIF1A, RDH13, CTH, ETS2, FAH, CLK4, RIMS4, FLJ12355, LDLR, AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 115 WARS, IFRD1, LRCH4, SLC1A4, FST, PPIF, ARHGEF2, PMAIP1, PBEF1, C14orf159, ATF4, FLJ90119, TGFBR3, DDX21, MUC8, TNFSF7, SPTLC2, KBTBD8, CIAS1, KIAA0476, NFKB1, DES /// FAM48A, ICAM1, INHBA, MARS, Clorf1 13, GRK6, TCF2, SLC7A1, TNFRSF10B, IER2, TFRC, SOS2, CARS, 5 HABIT /// LOC442496, KLHL24, SQSTM1, GIT1, IRS2, SARS, TRIM25, JUN, YRDC, ETS1, CTH, ABL2, CD274, FZD8, EREG, PFDN2, TMEM63B, DYRK3, GARS, RASSF8, CAMTA2, HOXC8, AARS, TBX3, RRAGC, BCAP29, TNFRSF10B, MCL1, PALM2-AKAP2, TMEM22, ZNF548, PCBP2, SLC1A4, FSTL3, TA-PP2C, PIM3, MAFG, NOL1, PEA15, ETS2, IQCG, BEX2, C12orf39, 10 LDLR, VEGF, CCNL1, LOC440069, SNAPC1, SLC27A5, MARS, ICAM1, AXUD1, KCNIP2, LOC146177 /// FLJ40941, GOT1, C11orf17 /// NUAK2, TTBK1, SNCA, NFRKB, GRB2, ADAMTS1, PALM2-AKAP2, CCNL1, JUN, SPRY4, SLC38A1, E2F7, MGC27165, IDS, SLC7A1, FLJ11021, KCNK5, GYPC, MYC, CACNG6, PHLDA1, INSIG1, FLJ13448, LOC202051, GALNT10, TFEB, ABL2, 15 MTHFD2, SERPINB8,TNPO2, MCF2L, SERTAD1, SPRY2, PHLDA1, SLC7A11, CXCL5, COMT, GTPBP2, RAB4B, ATXN7, OTUD5, VEGF, ADAMTS6, YARS, NAV3, SAMD4, C17orf32, SHMT2, CHIC2, ORAOV1, CREM, ALS2CL, AMIGO2, MGC19764, SFPQ, MGC11257, PLEKHM1, MMP28, SLC4A5, DNAJB9, ERRF11, FZD8, MGC4399, GUCA1B, ATP13A3, KIAA0020, XBP1, 20 ATP6V1B2, IGLV3-25, CHD4, GRB10, FLJ40089, CLDN19, NPC1, RIPK2, PLEKHF2, LOC283314, RSPO3, GSK3A, ANKRD1 1, WARS, GNPDA1, IGKC // IGKV1-5, RCL1, C9orf91, TIMM10, SLC1A4, ODC1, SLC38A1, EIF4EBP1, ZNF267, YRDC, CHD4, PER1, NFKBIE, INSIG1, FLJ11259, NCOA3, TNPO2, BAZ2A, SLC1A5, KRTAP2-1, PDE4DIP, EPB41L3, CITED2, JTV1, TA-PP2C, 25 METRNL, BCL10, Clorf19, PTP4A1, PDE4DIP, CPSF1, TIMM10, IGSF21, TM4SF1, CDK6, BANP, PHLDA1, PAPPA2, MGC1 7337, TNFRSF19L, ADAMTS10, CBFB, HERPUD1, RTTN, FLJ13855, SYNPO, NAV2, FLJ34208, DDX10, C6orf66, LOC56902, CHMP1B, HIPK2, H3F3B, NAV3, ELL2, NSUN5C, PLAUR, UCK2, PBEF1, TP53BP2, TEX10, B3GNT5, USP36, INHBA, SPIRE1, 30 CSTB, NSUN5C, TFPI2; or wherein the expression of the following genes is inhibited: FN1, ITGAV, LAMA4, LAMB2, LAMC1, LAMB1, LAMB1, LAMA4, LAMA5, LAMC1, LAMA2, LAMB1, LAMA3, SCAMPI, TICAM2, SCAMPI, TICAM2, SCAMPI, SCAMPI, CAMK 2B, D1, ICAM3,CEECAM1,ICAM5,SCAMP1, CAMK1G, CAMSAP1, MCAM, CAMTA1, 35 CKN1, ALCAM, DCAMKL2, CEACAM3, CAMK2D, CAMK2B, SCAMP5, CAMK4, NCAM1, CAMK2G, MYH9, MYH10, MYO1D, MYO5A, MYLK, MYO6, MYO5A, MYO1C, MYLK, MYO6, MYLC2PL, MYO10, MYO6, TPM3, MYO1C, BECN1, AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 116 MYO1E, TPM3, M-RIP, MYO1B, MYO10, MYO5A, M-RIP, MYO10, MYL6, MYOHD1, BECNI, TPM4, MYLK, MYH10, MYOHD1, LOC221875, LOC402643, MYO15B, LOC129285, MYH11, MYO1B, MYO1C, MYO9B, CDH13, CTNNAL1, CDH13, CDH12, CTNNB1, CDH5, CTNND1, CDH2, CTNNA1, CDH2, 5 PCDHB16, CTNNA1, CELSR2, PCDHB6, PCDHB7, CTNND2, PCDHGC3, PCDHGB4, PCDHGA8, PCDHGA12, PCDHGC5, PCDHGC4, PCDHGB7, PCDHGB6, PCDHGB5, PCDHGB3, PCDHGB2, PCDHGB1, PCDHGA11, PCDHGA10, PCDHGA9, PCDHGA7, PCDHGA6, PCDHGA5, PCDHGA4, PCDHGA3, PCDHGA2, PCDHGA1, CTNND1, CDH23, PCDHB12, PCDHB10, 10 PCDH18, CDH20, PCDH9, PCDHGA12, PCDHGA11, PCDHGA10, PCDHGA6, PCDHGA5, PCDHGA3, PCDH7, CDH18, CDH6, CCBE1, COL1OA1, COL12A1, COL13A1, COL18A1, COL1Al, COL21A1, COL4A1, COL4A2, COL4A5, COL4A6, COL5A1, COL5A2, COL6A1, COL6A2, COL6A3, COL9A1, MMP9, P4HA1, P4HA2, P4HB, PCOLCE, PCOLCE2, PCOTH, PLOD1, PLOD2, 15 PLOD3, CIB1, ILK, ITGA2, ITGA3, ITGA4, ITGA6, ITGAV, ITGB1, ITGB1BP1, ITGB2, ITGB5, ITGBL1, TNC, EMILIN1, ICAM1, HSPG2, HPSE, HS2ST1,SDC2,

37. The pharmaceutical composition of claim 25, further comprising a 20 pharmaceutically acceptable carrier or diluent.

38. The pharmaceutical composition of claim 37, wherein the said compound is present in a concentration of 0.01 ug/ml to 65ug/ml, or wherein the said compound is present in a concentration of 0.01 ug/ml to 30ug/ml, or wherein the 25 said compound is present in a concentration of 0.01 ug/ml to 1 Oug/ml, or wherein the said compound is present in a concentration of 0.01 ug/ml to 5ug/ml, or wherein the said compound is present in a concentration of 5 ug/ml to 1 0ug/ml, or wherein the said compound is present in a concentration of 0.1 ug/ml to 5ug/ml, or wherein the said compound is present in a concentration of 0.1 ug/ml 30 to 7.5ug/ml, or wherein the said compound is present in a concentration of 0.1 ug/ml to 1 0ug/ml, or wherein the said compound is present in a concentration of 0.1 ug/ml to 15ug/ml, or wherein the said compound is present in a concentration of 0.1 ug/ml to 20ug/ml, or wherein the said compound is present in a concentration of 0.1 ug/ml to 30ug/ml, or wherein the said compound is present 35 in a concentration of 1 ug/ml to 5ug/ml, or wherein the said compound is present in a concentration of 1 ug/ml to 7.5ug/ml, or wherein the said compound is present in a concentration of 1 ug/ml to 1 Oug/ml, or wherein the said compound AMENDED SHEET (ARTICLE 19) WO 2009/117196 PCT/US2009/034115 117 is present in a concentration of 1 ug/ml to 15ug/ml, or wherein the said compound is present in a concentration of 1 ug/ml to 20ug/ml, or wherein the said compound is present in a concentration of 1 ug/ml to 30ug/ml, or wherein the said compound is present in a concentration of 3 ug/ml to 5ug/ml, or wherein 5 the said compound is present in a concentration of 3 ug/ml to 7.5ug/ml, or wherein the said compound is present in a concentration of 3 ug/ml to 1 Oug/ml, or wherein the said compound is present in a concentration of 3 ug/ml to 15ug/ml, or wherein the said compound is present in a concentration of 3 ug/ml to 20ug/ml, or wherein the said compound is present in a concentration of 3 ug/ml to 30ug/ml. 10 AMENDED SHEET (ARTICLE 19)