CN101653447A - 三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 - Google Patents
三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 Download PDFInfo
- Publication number
- CN101653447A CN101653447A CN200910139993A CN200910139993A CN101653447A CN 101653447 A CN101653447 A CN 101653447A CN 200910139993 A CN200910139993 A CN 200910139993A CN 200910139993 A CN200910139993 A CN 200910139993A CN 101653447 A CN101653447 A CN 101653447A
- Authority
- CN
- China
- Prior art keywords
- application
- radix notoginseng
- type saponin
- pds
- chinese medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000007949 saponins Chemical class 0.000 title claims abstract description 28
- 229930182490 saponin Natural products 0.000 title claims abstract description 27
- 239000001397 quillaja saponaria molina bark Substances 0.000 title claims abstract description 21
- 230000000879 anti-atherosclerotic effect Effects 0.000 title claims abstract description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 24
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 11
- 210000002966 serum Anatomy 0.000 claims abstract description 9
- 208000035868 Vascular inflammations Diseases 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims description 30
- 241000180649 Panax notoginseng Species 0.000 claims description 29
- 235000003143 Panax notoginseng Nutrition 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 14
- 239000002552 dosage form Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 229940124549 vasodilator Drugs 0.000 claims description 5
- 239000003071 vasodilator agent Substances 0.000 claims description 5
- 230000008485 antagonism Effects 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 102000004895 Lipoproteins Human genes 0.000 claims description 2
- 108090001030 Lipoproteins Proteins 0.000 claims description 2
- 230000000304 vasodilatating effect Effects 0.000 claims description 2
- 238000002474 experimental method Methods 0.000 abstract description 13
- 235000012000 cholesterol Nutrition 0.000 abstract description 6
- 210000004204 blood vessel Anatomy 0.000 abstract description 3
- 230000036523 atherogenesis Effects 0.000 abstract 1
- 235000017709 saponins Nutrition 0.000 description 17
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 14
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 13
- YURJSTAIMNSZAE-HHNZYBFYSA-N ginsenoside Rg1 Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YURJSTAIMNSZAE-HHNZYBFYSA-N 0.000 description 13
- 210000004351 coronary vessel Anatomy 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 210000003725 endotheliocyte Anatomy 0.000 description 11
- 108010007622 LDL Lipoproteins Proteins 0.000 description 9
- 102000007330 LDL Lipoproteins Human genes 0.000 description 9
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 9
- 229930182494 ginsenoside Natural products 0.000 description 9
- 229940089161 ginsenoside Drugs 0.000 description 9
- TXEWRVNOAJOINC-UHFFFAOYSA-N ginsenoside Rb2 Natural products CC(=CCCC(OC1OC(COC2OCC(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CCC45C)C TXEWRVNOAJOINC-UHFFFAOYSA-N 0.000 description 9
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 208000006906 Vascular Ring Diseases 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- UFNDONGOJKNAES-UHFFFAOYSA-N Ginsenoside Rb1 Natural products CC(=CCCC(C)(OC1OC(COC2OC(CO)C(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CC(O)C45C)C UFNDONGOJKNAES-UHFFFAOYSA-N 0.000 description 6
- 208000035150 Hypercholesterolemia Diseases 0.000 description 6
- YURJSTAIMNSZAE-UHFFFAOYSA-N UNPD89172 Natural products C1CC(C2(CC(C3C(C)(C)C(O)CCC3(C)C2CC2O)OC3C(C(O)C(O)C(CO)O3)O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O YURJSTAIMNSZAE-UHFFFAOYSA-N 0.000 description 6
- GZYPWOGIYAIIPV-JBDTYSNRSA-N ginsenoside Rb1 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GZYPWOGIYAIIPV-JBDTYSNRSA-N 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 102000003945 NF-kappa B Human genes 0.000 description 5
- 108010057466 NF-kappa B Proteins 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- CBEHEBUBNAGGKC-UHFFFAOYSA-N ginsenoside Rg1 Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5CC(OC6OC(CO)C(O)C(O)C6O)C34C)C CBEHEBUBNAGGKC-UHFFFAOYSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 210000005087 mononuclear cell Anatomy 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 4
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 4
- 230000001476 alcoholic effect Effects 0.000 description 4
- 230000000923 atherogenic effect Effects 0.000 description 4
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 3
- 229930182837 (R)-adrenaline Natural products 0.000 description 3
- FBFMBWCLBGQEBU-GYMUUCMZSA-N 20-gluco-ginsenoside-Rf Natural products O([C@](CC/C=C(\C)/C)(C)[C@@H]1[C@H]2[C@H](O)C[C@H]3[C@](C)([C@]2(C)CC1)C[C@H](O[C@@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@H]1C(C)(C)[C@@H](O)CC[C@]31C)[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 FBFMBWCLBGQEBU-GYMUUCMZSA-N 0.000 description 3
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 3
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000003463 adsorbent Substances 0.000 description 3
- 230000000489 anti-atherogenic effect Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 150000002009 diols Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229960005139 epinephrine Drugs 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000024883 vasodilation Effects 0.000 description 3
- 230000001196 vasorelaxation Effects 0.000 description 3
- RWXIFXNRCLMQCD-JBVRGBGGSA-N (20S)-ginsenoside Rg3 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RWXIFXNRCLMQCD-JBVRGBGGSA-N 0.000 description 2
- FBFMBWCLBGQEBU-RXMALORBSA-N (2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5s,6r)-2-[[(3s,5r,6s,8r,9r,10r,12r,13r,14r,17s)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-[(2s)-6-methyl-2-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhept-5-en-2-yl]-2,3,5,6,7,9,11,12,13,15,16,17-dodecah Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FBFMBWCLBGQEBU-RXMALORBSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- HYPFYJBWSTXDAS-UHFFFAOYSA-N Ginsenoside Rd Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C4CCC5C(C)(C)C(CCC5(C)C4CC(O)C23C)OC6OC(CO)C(O)C(O)C6OC7OC(CO)C(O)C(O)C7O)C HYPFYJBWSTXDAS-UHFFFAOYSA-N 0.000 description 2
- AGBCLJAHARWNLA-DQUQINEDSA-N Ginsenoside Rg2 Natural products O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@@](C)(O)CCC=C(C)C)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O AGBCLJAHARWNLA-DQUQINEDSA-N 0.000 description 2
- 108010023302 HDL Cholesterol Proteins 0.000 description 2
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 244000131316 Panax pseudoginseng Species 0.000 description 2
- 235000003181 Panax pseudoginseng Nutrition 0.000 description 2
- VSWDORGPIHIGNW-UHFFFAOYSA-N Pyrrolidine dithiocarbamic acid Chemical compound SC(=S)N1CCCC1 VSWDORGPIHIGNW-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- HMFHBZSHGGEWLO-QMKXCQHVSA-N alpha-L-arabinofuranose Chemical compound OC[C@@H]1O[C@@H](O)[C@H](O)[C@H]1O HMFHBZSHGGEWLO-QMKXCQHVSA-N 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 239000012531 culture fluid Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- PFSIGTQOILYIIU-UHFFFAOYSA-N ginsenoside Rb3 Natural products CC(=CCCC(C)(O)C1CCC2(C)C3CCC4C(C)(C)C(CCC4(C)C3CC(OC5OC(COC6OCC(O)C(O)C6O)C(O)C(O)C5O)C12C)OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C PFSIGTQOILYIIU-UHFFFAOYSA-N 0.000 description 2
- PWAOOJDMFUQOKB-WCZZMFLVSA-N ginsenoside Re Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@](C)(CCC=C(C)C)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O PWAOOJDMFUQOKB-WCZZMFLVSA-N 0.000 description 2
- AOGZLQUEBLOQCI-UHFFFAOYSA-N ginsenoside-Re Natural products CC1OC(OCC2OC(OC3CC4(C)C(CC(O)C5C(CCC45C)C(C)(CCC=C(C)C)OC6OC(CO)C(O)C(O)C6O)C7(C)CCC(O)C(C)(C)C37)C(O)C(O)C2O)C(O)C(O)C1O AOGZLQUEBLOQCI-UHFFFAOYSA-N 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- SHCBCKBYTHZQGZ-CJPZEJHVSA-N protopanaxatriol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2[C@@H](O)C[C@@]3(C)[C@]4(C)CC[C@H]([C@@](C)(O)CCC=C(C)C)[C@H]4[C@H](O)C[C@@H]3[C@]21C SHCBCKBYTHZQGZ-CJPZEJHVSA-N 0.000 description 2
- BBEUDPAEKGPXDG-UHFFFAOYSA-N protopanaxatriol Natural products CC(CCC=C(C)C)C1CCC2(C)C1C(O)CC3C4(C)CCC(O)C(C)(C)C4C(O)CC23C BBEUDPAEKGPXDG-UHFFFAOYSA-N 0.000 description 2
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- UOJAEODBOCLNBU-UHFFFAOYSA-N vinaginsenoside R4 Natural products C1CC(C2(CC(O)C3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O UOJAEODBOCLNBU-UHFFFAOYSA-N 0.000 description 2
- AGBCLJAHARWNLA-UHFFFAOYSA-N (20R)-ginsenoside Rg2 Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C3C(C)(C)C(O)CCC3(C)C3C(C4(CCC(C4C(O)C3)C(C)(O)CCC=C(C)C)C)(C)C2)OC(CO)C(O)C1O AGBCLJAHARWNLA-UHFFFAOYSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- 101150019464 ARAF gene Proteins 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- UZIOUZHBUYLDHW-MSJHMJQNSA-N Ginsenoside Rf Natural products O([C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@@H]1O[C@@H]1[C@H]2C(C)(C)[C@@H](O)CC[C@]2(C)[C@@H]2[C@](C)([C@@]3(C)[C@H]([C@@H](O)C2)[C@@H]([C@@](O)(CC/C=C(\C)/C)C)CC3)C1)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 UZIOUZHBUYLDHW-MSJHMJQNSA-N 0.000 description 1
- XIRZPICFRDZXPF-UHFFFAOYSA-N Ginsenoside Rg3 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(CC(O)C3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O XIRZPICFRDZXPF-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- -1 TC) Chemical compound 0.000 description 1
- YQKCHRBAJSATCG-UHFFFAOYSA-N UNPD30744 Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC(C)(CCC=C(C)C)C2C3C(C4(CCC5C(C)(C)C(OC6C(C(O)C(O)C(CO)O6)OC6C(C(O)C(O)C(CO)O6)O)CCC5(C)C4CC3O)C)(C)CC2)O1 YQKCHRBAJSATCG-UHFFFAOYSA-N 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- SRBFZHDQGSBBOR-KKQCNMDGSA-N beta-D-xylose Chemical compound O[C@@H]1CO[C@@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-KKQCNMDGSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 238000003352 cell adhesion assay Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- CNHRRMQBWQJRPN-UHFFFAOYSA-N chikusetsusaponin LM5 Natural products C1CC(C2(CC(O)C3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OC(CO)C(O)C1O CNHRRMQBWQJRPN-UHFFFAOYSA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- WQMLFJWIKARBFW-BKKMTDGVSA-N evomonoside Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@H](CC[C@H]2[C@]3(CC[C@@H]([C@@]3(C)CC[C@H]32)C=2COC(=O)C=2)O)[C@]3(C)CC1 WQMLFJWIKARBFW-BKKMTDGVSA-N 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 150000002243 furanoses Chemical class 0.000 description 1
- 239000008246 gaseous mixture Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- NODILNFGTFIURN-GZPRDHCNSA-N ginsenoside Rb2 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1OC[C@H](O)[C@H](O)[C@H]1O NODILNFGTFIURN-GZPRDHCNSA-N 0.000 description 1
- NODILNFGTFIURN-USYOXQFSSA-N ginsenoside Rb3 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O NODILNFGTFIURN-USYOXQFSSA-N 0.000 description 1
- JDCPEKQWFDWQLI-LUQKBWBOSA-N ginsenoside Rc Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@@H](CO)[C@H](O)[C@H]1O JDCPEKQWFDWQLI-LUQKBWBOSA-N 0.000 description 1
- UZIOUZHBUYLDHW-XUBRWZAZSA-N ginsenoside Rf Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@H]2C(C)(C)[C@@H](O)CC[C@]2(C)[C@H]2C[C@@H](O)[C@H]3[C@@]([C@@]2(C1)C)(C)CC[C@@H]3[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZIOUZHBUYLDHW-XUBRWZAZSA-N 0.000 description 1
- UVBLDLGZDSGCSN-UHFFFAOYSA-N ginsenoside-Rb3 Natural products C1=CC2C3(C)CCC(O)C(C)(C)C3CCC2(C)C2(C)CCC34CCC(C)C(C)C4C21OC3=O UVBLDLGZDSGCSN-UHFFFAOYSA-N 0.000 description 1
- SPFXZQZPHXUJSR-UHFFFAOYSA-N ginsenoside-Rc Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1OC2OC(CO)C(O)C2O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CCC45C)C SPFXZQZPHXUJSR-UHFFFAOYSA-N 0.000 description 1
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000004987 nonapoptotic effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- JURZHOVRCOWZFN-UHFFFAOYSA-N notoginsenoside R1 Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5C(CC34C)OC6OC(COC7OCC(O)C(O)C7O)C(O)C(O)C6O)C JURZHOVRCOWZFN-UHFFFAOYSA-N 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004279 orbit Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- 108700022737 rat Fat1 Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 230000015590 smooth muscle cell migration Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了中药三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物的应用，通过实验证明，三七中原人参二醇型皂苷能够有效对抗血管炎症，明显降低血清总胆固醇含量，提高血清中HDL，舒张血管，降低动脉粥样硬化指数，是一种很有潜力的抗动脉粥样硬化药物。
Description
技术领域
本发明涉及医药技术领域，具体是中药三七中的原人参二醇型皂苷在制备抗动脉粥样硬化药物的应用。
背景技术
近年来，随着我国经济的发展，心脑血管疾病的发病率和死亡率逐年增加，已被称为危害人类健康和生命的头号杀手。动脉粥样硬化(Atherosclerosis，AS)为多种心脑血管疾病的病理基础，主要累及大中动脉，可导致心、脑等多个重要器官的组织缺血和坏死，引发心肌梗死、脑梗塞等。动脉粥样硬化是一个复杂的过程，包括内皮损伤，低密度脂蛋白(LDL)氧化修饰，单核细胞黏附，平滑肌细胞增殖及纤维斑块形成。在多种危险因素(高血压、高脂血症、糖尿病、衰老、病毒、吸烟和酗酒等)的作用下，动脉内皮损伤坏死剥脱，产生和释放各种细胞粘附分子和生长因子并在它们的作用下，血小板和单核细胞在该处粘附，进而单核细胞进入内皮下间隙转化为巨噬细胞；中膜平滑肌细胞移行至内膜，并大量增殖或凋亡；巨噬细胞和平滑肌细胞摄取胆固醇转化为泡沫细胞，形成AS的早期病变即脂纹。在此基础上，逐步发展为由坏死细胞碎片、胆固醇及其酯、血管平滑肌、巨噬细胞、T-淋巴细胞以及致密的纤维组织构成的纤维斑块。斑块形成后不稳定因素导致纤维帽破裂，形成血管堵塞，淤滞等。
三七为五加科人参属植物三七(Panax notoginseng(Burk.)F.H.Chen)的干燥根，有散瘀止痛，消肿定痛的功效。现代药理学表明，三七对血液系统、心血管系统、免疫系统均有不同的作用。皂苷为三七的主要活性成分，包括三七皂苷R1，人参皂苷Rb1，Rg1，Re和Rd等。通过之前的体内药理学研究已经发现三七总皂苷(PNS)为三七抗动脉粥样硬化的主要活性成分。而三七总皂苷又可进一步分为三醇型总皂苷(PTS)和二醇型总皂苷(PDS)两大类，分别以人参皂苷Rg1(ginsenoside Rg1)和人参皂苷Rb1(ginsenoside Rb1)为主要单体成分。本发明中对三七的提取物：i)总皂苷提取物(PNS)；ii)人参二醇型皂苷提取物(PDS)；iii)人参三醇型皂苷提取物(PTS)的抗动脉粥样硬化作用进行研究。
发明内容
本发明的目的是提供一种能从各个方面防治动脉粥样硬化的药物。
本发明的目的是这样实现的：中药三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物的应用。
所述抗动脉粥样硬化包括对抗血管炎症、降低血清胆固醇含量或舒张血管中一种或以上。
中药三七中原人参二醇型皂苷在制备治疗血管炎症的药物的应用。
中药三七中原人参二醇型皂苷在制备降低血清总胆固醇含量，提高血清中高密度脂蛋白含量的药物的应用。
中药三七中原人参二醇型皂苷在制备舒张血管的药物的应用。
所述的药物剂型为医学上认可的任何一种剂型。
所述的药物剂型为粉剂、注射液、胶囊、片剂或口服液。
为系统的研究三七的抗动脉粥样硬化效果，首先比较了PNS、PTS和PDS在人冠状动脉内皮细胞(Human Coronary Artery Endothelial Cells，HCAEC)体外模型上的抗炎作用。实验采用肿瘤坏死因子α(TNF-α)刺激的HCAEC表达黏附分子，再给药保护。用细胞黏附实验观测PNS、PTS、PDS对THP-1单核细胞黏附TNF-α刺激的HCAEC的影响；用cell-ELISA检测PNS、PTS和PDS对细胞内黏附分子(ICAM-1)和细胞间黏附分子(VCAM-1)的抑制作用；另外，real-time PCR和Western Blotting用于观察PNS、PTS和PDS对ICAM-1和VCAM-1基因和蛋白表达的抑制。
另外，通过采用体内模型，观测了PNS、PTS和PDS对膳食诱导的高胆固醇血症大鼠的血脂调节作用。SD大鼠随机分为5组，正常组、模型组、PNS给药组、PTS给药组。模型组和给药组均给予富含胆固醇的饲料4周，给药组每天灌胃给一定浓度的PNS、PTS或PDS。检测血清总胆固醇(total cholesterol，TC)、甘油三酯(triglyceride，TG)、葡萄糖(Glucose)、高密度脂蛋白胆固醇(HDL-c)和低密度脂蛋白胆固醇(LDL-c)的含量。
此外还考察了PNS、PTS和PDS的血管舒张作用。实验中，苯丙肾上腺素预处理的大鼠胸主动脉环，造成血管舒张。给PNS、PTS和PDS处理后，观察它们的舒张血管作用。
附图说明
图1是三七的HPLC-ELSD图谱：(A)为混合标准品，(B)三七甲醇提取物，1为三七皂苷R1，2-11分别是人参皂苷Rg1，Re，Rf，Rb1，Rg2，Rc，Rb2，Rb3，Rd和Rg3；
图2是11种三七皂苷化学结构：1-11分别是三七皂苷R1、Rg1、Re、Rf、Rb1、Rg2、Rc、Rb2、Rb3和Rg3；Glc，β-D-glucose；Rha，α-L-rhamnose；Arap，α-L-arabinose(pyranose)；Araf，α-L-arabinose(furanose)；Xyl，β-D-xylose；
图3是用DS-401大孔树脂分离得到的20(S)-原人参二醇型三七皂苷和20(S)-原人参三醇型三七皂苷的HPLC图谱：1、三七皂苷R1，2-10分别是人参皂苷Rg1，Re，Rf，Rb1，Rg2，Rc，Rb2，Rb3和Rd，11为三七皂苷K；
图4是显示不同的皂苷部分和由三七分离得到的人参皂苷单体对THP-1与被TNF-α刺激的HCAEC细胞的粘附影响的图表：HCAECs用不同的皂苷部分和人参皂苷单体预处理24小时，接着再用10ng/ml的TNF-α刺激6小时，其中，以NF-κB的抑制剂PDTC作为阳性对照；数据±SEM来自3次不同的实验；与对照组比较##P＜0.01；与TNF-α组比较*P＜0.05，**P＜0.01；
图5是显示三七皂苷及其人参皂苷对被TNF-α刺激的HCAECs的膜蛋白(a)ICAM-1和(b)VCAM-1表达的抑制作用的图表：HCAECs用特定浓度的PNS，PDS，PTS，Rb1和Rg1预处理24小时，然后加入10ng/ml的TNF-α再培养6小时；其中，PDTC作为阳性对照；数据±SEM来自3次不同的实验；与对照组比较##P＜0.01；与TNF-α组比较*P＜0.05，**P＜0.01；
图6是显示三七皂苷部分及其人参皂苷对(a)ICAM-1和(b)VCAM-1粘附小分小子的mRNA水平的影响的图表：HCAECs先用不同浓度的PNS，PDS，PTS，人参皂苷Rb1和Rg1预处理24小时，再加入10ng/ml的TNF-α培养4小时。分离得到的总RNA量以及ICAM-1，VCAM-1与GAPDH的mRNA量用RT-PCR进行定量。GAPDH是一保守基因；数据±SEM来自3次不同的实验；与对照组比较##P＜0.01；与TNF-α组比较*P＜0.05，**P＜0.01；
图7显示的是三七皂苷及其人参皂苷对被TNF-α刺激的HCAECs膜蛋白ICAM-1和VCAM-1表达的影响：HCAECs先用不同浓度的三七皂苷及其人参皂苷预处理24小时，再加入10ng/ml的TNF-α培养6小时；处理过后，从HCAECs中提取到的总蛋白和膜蛋白ICAM-1与VCAM-1用western blot进行分析；
图8显示的是三七皂苷及其人参皂苷对NF-κB/p65核转运的影响：HCAECs分别用300μg/ml的PNS，50μg/ml的PDS，100μg/ml的PTS，50μM的Rb1和30μM的Rg1预处理24小时，再加入10ng/ml的TNF-α培养0.5小时；通过观察有Alexa fluor 488绿色荧光标记的NF-κB/p65抗体来检测NF-κB/p65的表达(放大倍数为400)；
表1是实施例3对比试验中大鼠血脂水平对比数据表；
图9是不同药物处理的胸主动脉环血管张力对乙酰胆碱的量效曲线图；数据±SEM来自4～7次不同的实验；与对照组比较**p＜0.01；
图10是动脉粥样硬化指数，数据±SEM来自5～7次不同的实验；与对照组比较##p＜0.01 and ###p＜0.001；与高胆固醇饮食组比较***p＜0.001。
具体实施方式
发明所述的含三七中原人参二醇型皂苷药物的制备可参考常规的药物配置方法，在知道了所需药物的给药剂量以后，药物的配置是本技术领域人员所熟知的。药物剂型为医学上认可的任何一种剂型，例如为粉剂、注射液、胶囊、片剂或口服液。
实施例1：三醇型总皂苷(PTS)和二醇型总皂苷(PDS)的分离鉴定
为了进一步研究三七皂苷的抗动脉粥样硬化活性成分，需对三七总皂苷进行分离。本发明提供一个能简便有效的利用大孔吸附树脂分离PNS的方法。依次用纯水，一定浓度的乙醇和高浓度的乙醇洗脱装了PNS的大孔吸附树脂分离柱，能依次得到高极性物质(如多糖、氨基酸)、PTS、PDS。
三七药材水提物或三七药材醇提物水溶部位或三七总皂苷PNS[本试验PNS购自万方(玉溪，中国云南)]经苯乙烯为骨架的大孔吸附树脂吸附后(原料与树脂比为1∶8-20；w/w)，先用水或者25％以下的乙醇溶液洗脱1-3个柱体积，再用30-40％的乙醇溶液洗脱1-5个柱体积，最后用50-95％的乙醇溶液洗脱1-5个柱体积。分别回收30-40％和50-95％乙醇溶液洗脱物，即得三醇型总皂苷(PTS)和二醇型总皂苷(PDS)。Rb1和Rg1用制备液相色谱分离纯化，分离得到的三七皂苷类成分用对应的标准品比较保留时间和质谱的图谱来确认，见图1-3，PNS，PDS和PTS用Mill-Q水配置检验浓度为1mg/ml，Rb1和Rg1浓度为1μM的溶液，并用0.22μm的滤膜(Agilent Technologies)过滤。
实施例2：比较PNS，PTS和PDS在人冠状动脉内皮细胞(Human Coronary ArteryEndothelial Cells，HCAEC)体外模型上的抗炎作用
人冠状动脉内皮细胞培养人冠状动脉内皮细胞(HCAECs，from Cambrex Corporation，NJ，USA)采用EGM-2MV培养液培养，其中包含集中细胞生长必需因子(SingleQuots试剂盒，包含Hydrocortisone，hFGF，VEGF，IGF-1，Ascorbic acid，hEGF，R3-IGF-1 and GA)(Cambrex)和5％胎牛血清，培养温度37℃，培养气体含5％CO2.细胞长满视野85％～90％时可用于实验，2～6代细胞可用。THP-1细胞从美国ATCC公司购买(ATCC；Rockville，MD，USA)，用RPMI-1640培养液培养(GIBCO，Grand Island，NY)其中富含10％(v/v)热灭活胎牛血清(FBS)。
细胞黏附实验(cell adhesion assay)细胞黏附实验采用被荧光染色物质Calcein-AM(10μM)染色30分钟作为标记了的THP-1细胞完成。人冠状动脉内皮细胞(5×103cells/well)于不同浓度的PNS，PDS，PTS，Rg1 and Rb1混合种于96孔板，37℃培养24小时，然后用10ng/mlTNF-α刺激6小时。然后将Calcein-AM标记了的THP-1细胞(5×103cells/well)与人冠状动脉内皮细胞共同培养30分钟。用多功能荧光读数仪(fluorescence multiwell plate reader，Wallac 1420，Germany)读数，激发光和放射光检测波长485和530nm。用PBS清洗细胞3次，以去除未黏附的THP-1细胞，并再次测量吸收值。结果如图4所示。
细胞酶联免疫荧光法实验(cell-ELISA) 人冠状动脉内皮细胞表面ICAM-1和VCAM-1Cell的表达用细胞酶联免疫荧光法检测。人冠状动脉内皮细胞(5×103cells/well)于不同浓度PNS，PDS，PTS，Rg1 and Rb1混合种于96孔板，37℃培养24小时，然后用溶解于05％FBS的10ng/ml TNF-α刺激6小时。在用冷却的PBST(含0.05％吐温-20的PBS)和80％乙醇混合液冰浴处理15分钟。加入含1％BSA的PBS减少非特异性结合。用PBST清洗3次后，在37℃下将细胞与anti-ICAM-1和anti-VCAM-1单抗混合培养1小时，再用PBST清洗后，加入过氧化物酶标记的羊抗-鼠二抗。再次用PBST清洗后，向其中加入底物显色液，在暗室中培养15分钟，最后用50μl/well的2N H2SO4终止反应。用多功能荧光读数仪在490nm下测量荧光吸收值。结果如图5所示。
RNA提取和即时聚合酶链反应(real-time PCR)分析试验 内皮细胞中总RNA提取采用试剂盒RNeasy mini Kit(QIAGEN，Valencia，CA)完成.根据说明书，在即时RT-PCR(Invitrogen Corp.，Carlsbad，CA)系统上采用SuperScript IIIFirst-strand合成系统完成，每个提取样品中将有0.7μg的mRNA被反转录成cDNA。GAPDH，VCAM-1 andICAM-1(Roche，Foster City，CA，USA)用的寡核苷酸引物和TaqMan
探针由AppliedBiosystems设计和提供，通用PCR master mix从TaqMan购买，用于定量检测。所有的待测样品都依照GAPDH含量进行均一化，并重复测量三次。结果如图6所示。
Western免疫印迹法(Western blotting) 人冠状动脉内皮细胞(50×104cells/dish)于不同浓度的PNS，PDS，PTS，Rg1 and Rb1混合种于96孔板，37℃培养24小时，然后用溶解于05％FBS的10ng/ml TNF-α刺激6小时。然后将细胞用含有1％PMSF，1％蛋白酶抑制剂混合物和1％原钒酸钠的RIPA裂解液(RIPA lysis buffer，Santa Cruz，CA)裂解。在冰浴处理30分钟后，在4℃、11419×g下离心30分钟去除细胞残余物，采用BCA蛋白试剂盒(PIERCE，Rockford，IL)测量蛋白含量。将裂解物均分，上样到10％SDS-PAGE(with 5％ stacking gel)并转移到PVDF膜(Bio-Rad，Hercules，CA)上。在膜上加入抗ICAM-1(1∶1000)and VCAM-1(1∶500)的单抗，再分别加入1∶7500和1∶2000稀释的辣根过氧化物酶修饰的二抗。最后按说明书加入ECL advanced检测试剂盒(Amersham，UK)显影。结果如图7所示。
免疫染色法(Immunostaining assay) 将人冠状动脉内皮细胞种于24孔板，并用80％乙醇固定10分钟。将细胞与鼠抗P65(1∶100)单抗混合室温下培养1小时，再用抗鼠IgG Alexa488抗体(1∶100)混合培养30分钟。PBS清洗3次后，再加入propidium iodide(PI)(1∶1000)混合10分钟。最后用荧光显微镜拍照并进行图形处理。结果如图8所示。
单核细胞黏附实验、cell-ELISA、real-time PCR和western blotting的结果都表明PNS、PTS和PDS都能不多程度的缓解TNF-α刺激的HCEAC的炎症反应，且PDS能比PNS和PTS更有效的对抗血管炎症。结果还表明，虽然人参皂苷Rb1是PDS的主要成分，但它的抗炎效果远远低于PDS。这提示PDS中的各个成分间可能存在协同作用。对PNS、PTS和PDS抗血管炎症作用的机制研究表明，抑制NF-κB通路是他们发挥抗炎作用的原因。这些结果表明，PNS、PTS和PDS能够不同程度对抗血管炎症，保护血管内皮细胞，从而对抗动脉粥样硬化的形成。
实施例3：采用体内模型，观测PNS，PTS和PDS对膳食诱导的高胆固醇血症大鼠的血脂调节、血管舒张作用和动脉粥样硬化指数的影响
高胆固醇是引发动脉粥样硬化及相关心血管疾病的主要危险因子之一。因此，通过采用体内模型，观测了PNS、PTS和PDS对膳食诱导的高胆固醇血症大鼠的血脂调节作用。
1 动物 SPF级健康雄性SD大鼠，220～250g，由广州中医药大学试验动物中心提供，动物合格证号：0016120。
2 药品与仪器 总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)检测试剂盒均购自北京中生北控；全自动生化仪为ALYCON。
3 动物分组与模型的建立 SD大鼠，适应环境1周后，眼眶取血，测定血脂水平，血脂水平不正常动物剔除。然后随机分为3组，每组8只。正常组给予正常饲料(蛋白质14％，脂肪10％，碳水化合物76％)；模型组和治疗组给予添加有2％胆固醇、1％胆酸、5％花生油的饲料；治疗组每天灌服不同剂量PNS、PDS、PTS溶液。
4 血脂测定 4周后，禁食过夜，乙醚麻醉后心脏取血。在全自动生化仪上测定总胆固醇TC、甘油三脂TG、高密度脂蛋白HDL和低密度脂蛋白LDL，结果见表1。
5 由于血管舒张也是防治动脉粥样硬化的一重要手段，因此还考察了PNS、PTS和PDS的血管舒张作用。血管环制备及张力测定：动物放血后，迅速开胸，分离出胸主动脉，置于95％O2和5％CO2混合气预饱和的4℃K-H液中。小心剔除血管周围结缔组织，剪成3～4mm的血管环。用棉签磨擦血管环内表面去除内皮细胞，以制备内皮去除的血管环。将血管环悬挂于预置10ml K-H液的浴槽内，37℃恒温，持续通以95％O2和5％CO2混合气体。血管环静息张力2g，平衡60min，期间每15min换液一次。苯丙肾上腺素预处理大鼠胸主动脉环，造成血管舒张。给PNS、PTS和PDS处理后，观察它们的舒张血管作用。用PowerLab生物功能实验系统记录血管环张力变化。结果见图9。
结果表明，PNS、PTS和PDS均能显著降低高胆固醇膳食引起的血清胆固醇升高，提高LDL含量，降低动脉粥样硬化指数，且PNS、PDS的效果明显优于PTS。PNS、PTS和PDS也均能有效的缓解苯丙肾上腺素诱导的血管紧张。这些数据表明PNS和PDS能够降低血清胆固醇，降低动脉粥样硬化发生的危险。
结论：PDS能够有效对抗血管炎症，明显降低血清总胆固醇含量，提高血清中HDL，舒张血管，降低动脉粥样硬化指数。这些数据表明PDS能从各个方面防治动脉粥样硬化，是一种很有潜力的抗动脉粥样硬化药物。
Claims (7)
1.中药三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物的应用。
2.根据权利要求1所述的中药三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物的应用，其特征在于：所述抗动脉粥样硬化包括对抗血管炎症、降低血清胆固醇含量或舒张血管中一种或以上。
3.中药三七中原人参二醇型皂苷在制备治疗血管炎症的药物的应用。
4.中药三七中原人参二醇型皂苷在制备降低血清总胆固醇含量，提高血清中高密度脂蛋白含量的药物的应用。
5.中药三七中原人参二醇型皂苷在制备舒张血管的药物的应用。
6.根据权利要求1-5中任一权利要求所述的中药三七中原人参二醇型皂苷的应用，其特征在于：所述的药物剂型为医学上认可的任何一种剂型。
7.根据权利要求1-5中任一权利要求所述的中药三七中原人参二醇型皂苷的应用，其特征在于：所述的药物剂型为粉剂、注射液、胶囊、片剂或口服液。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910139993A CN101653447A (zh) | 2009-07-14 | 2009-07-14 | 三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910139993A CN101653447A (zh) | 2009-07-14 | 2009-07-14 | 三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101653447A true CN101653447A (zh) | 2010-02-24 |
Family
ID=41708049
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910139993A Pending CN101653447A (zh) | 2009-07-14 | 2009-07-14 | 三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101653447A (zh) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106632570A (zh) * | 2016-09-19 | 2017-05-10 | 李晓辉 | 二醇型人参皂苷衍生物及其制备方法和应用 |
| CN108309999A (zh) * | 2018-05-04 | 2018-07-24 | 南方医科大学 | 一种防治动脉粥样硬化的药物组合物 |
| CN110680822A (zh) * | 2019-11-15 | 2020-01-14 | 邹澄 | 一种人参二醇、人参三醇的pcc氧化产物的应用 |
| CN111821330A (zh) * | 2019-04-19 | 2020-10-27 | 香港大学 | 三七水提取物在制备降血脂产品中的用途 |
-
2009
- 2009-07-14 CN CN200910139993A patent/CN101653447A/zh active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106632570A (zh) * | 2016-09-19 | 2017-05-10 | 李晓辉 | 二醇型人参皂苷衍生物及其制备方法和应用 |
| CN106632570B (zh) * | 2016-09-19 | 2018-07-17 | 李晓辉 | 二醇型人参皂苷衍生物及其制备方法和应用 |
| RU2730495C1 (ru) * | 2016-09-19 | 2020-08-24 | Арми Медикал Юниверсити | Производное гинзенозида панаксдиолового типа, способ его получения и применения |
| US11091511B2 (en) | 2016-09-19 | 2021-08-17 | Army Medical University | Panaxdiol-type ginsenoside derivative, preparation method therefor and use thereof |
| CN108309999A (zh) * | 2018-05-04 | 2018-07-24 | 南方医科大学 | 一种防治动脉粥样硬化的药物组合物 |
| CN111821330A (zh) * | 2019-04-19 | 2020-10-27 | 香港大学 | 三七水提取物在制备降血脂产品中的用途 |
| CN110680822A (zh) * | 2019-11-15 | 2020-01-14 | 邹澄 | 一种人参二醇、人参三醇的pcc氧化产物的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Saponins and flavonoids from adzuki bean (Vigna angularis L.) ameliorate high-fat diet-induced obesity in ICR mice | |
| Dashora et al. | Antitumor activity of Dendrophthoe falcata against ehrlich ascites carcinoma in swiss albino mice | |
| Wan et al. | Panax notoginseng reduces atherosclerotic lesions in ApoE-deficient mice and inhibits TNF-α-induced endothelial adhesion molecule expression and monocyte adhesion | |
| CN103222988B (zh) | 一种美洲大蠊提取物及其制备方法和应用 | |
| Kimura et al. | Anti-obesity effects of highly polymeric proanthocyanidins from seed shells of Japanese horse chestnut (Aesculus turbinata Blume) | |
| Park et al. | Antidiabetic activity of fruits and vegetables commonly consumed in Korea: Inhibitory potential against α-glucosidase and insulin-like action in vitro | |
| Caldeira et al. | Bioguided chemical characterization of pequi (Caryocar brasiliense) fruit peels towards an anti-diabetic activity | |
| Peng et al. | Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats | |
| CN101653447A (zh) | 三七中原人参二醇型皂苷在制备抗动脉粥样硬化药物中的应用 | |
| Kim et al. | Orostachys japonicus exerts antipancreatic cancer activity through induction of apoptosis and cell cycle arrest in PANC‐1 cells | |
| Hajizadeh-Sharafabad et al. | Effect of Gundelia tournefortii L. extract on lipid profile and TAC in patients with coronary artery disease: A double-blind randomized placebo controlled clinical trial | |
| CN102281888A (zh) | Gip升高抑制剂 | |
| Felemban et al. | A pilot study of the effects of ajwa date seed extract in a diabetic animal with parallel observations on human subjects | |
| Li et al. | Exploring the active compounds and potential mechanism of the anti-nonalcoholic fatty liver disease activity of the fraction from Schisandra chinensis fruit extract based on multi-technology integrated network pharmacology | |
| WO2024114248A1 (zh) | 一种柑橘属果实提取物及其制备方法与应用 | |
| Malematja et al. | Potential hypoglycaemic and antiobesity effects of Senna italica leaf acetone extract | |
| Librandi et al. | Effect of the extract of the tamarind (Tamarindus indica) fruit on the complement system: studies in vitro and in hamsters submitted to a cholesterol-enriched diet | |
| US20120071431A1 (en) | Platycodin Radix Extracts, and Their Use in Treating Disease Conditions Associated with Angiogenesis | |
| Idakwoji et al. | Co-administeration of ethanolic leaf extract of moringa oleifera and metformin improves glucose, lipid and protein profiles of diabetic wistar rats | |
| Mishra et al. | An overview on Panax ginseng | |
| Madhavan et al. | PHARMACOLOGICAL AND ANTI CANCER ACTIVITY OF Ipomoea sepiaria METHANOLIC EXTRACT AGAINST PC-3 CELL LINE | |
| Srivastava et al. | Antidiabetic activity of the stem extracts of Cissus quadrangularis Linn | |
| CN111920849B (zh) | 一种中药组合物及包含该中药组合物的中药制剂 | |
| Hasim et al. | Pancreatic lipase inhibition activity in lipid absorption using traditional plants: A systematic review and meta-analysis | |
| CN110652505B (zh) | 南湖菱壳多酚提取物在制备用于抗her-2过表达型乳腺癌药物中的用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20100224 |