CN111574579B - 达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用 - Google Patents
达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用 Download PDFInfo
- Publication number
- CN111574579B CN111574579B CN202010571725.1A CN202010571725A CN111574579B CN 111574579 B CN111574579 B CN 111574579B CN 202010571725 A CN202010571725 A CN 202010571725A CN 111574579 B CN111574579 B CN 111574579B
- Authority
- CN
- China
- Prior art keywords
- group
- compound
- saponin
- dammarane
- compounds
- 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.)
- Active
Links
- OORMXZNMRWBSTK-LGFJJATJSA-N dammarane Chemical compound C1CCC(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@H]([C@H](C)CCCC(C)C)[C@H]4CC[C@@H]3[C@]21C OORMXZNMRWBSTK-LGFJJATJSA-N 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 230000002218 hypoglycaemic effect Effects 0.000 title claims abstract description 18
- 229940124599 anti-inflammatory drug Drugs 0.000 title claims abstract description 10
- 239000001397 quillaja saponaria molina bark Substances 0.000 title abstract description 54
- 229930182490 saponin Natural products 0.000 title abstract description 54
- 150000007949 saponins Chemical class 0.000 title abstract description 53
- -1 triterpenoid saponin compounds Chemical class 0.000 claims abstract description 80
- 241000233779 Cyclocarya paliurus Species 0.000 claims abstract description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 44
- 239000000284 extract Substances 0.000 claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229930182493 triterpene saponin Natural products 0.000 claims abstract description 14
- 238000005406 washing Methods 0.000 claims abstract description 6
- 239000011347 resin Substances 0.000 claims abstract description 5
- 229920005989 resin Polymers 0.000 claims abstract description 5
- 230000002829 reductive effect Effects 0.000 claims abstract description 4
- 238000010992 reflux Methods 0.000 claims abstract description 4
- 238000001179 sorption measurement Methods 0.000 claims abstract description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000000706 filtrate Substances 0.000 claims abstract description 3
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 67
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 238000010898 silica gel chromatography Methods 0.000 claims description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 150000008130 triterpenoid saponins Chemical class 0.000 claims description 17
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 229940125782 compound 2 Drugs 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 239000012071 phase Substances 0.000 claims description 14
- 230000002441 reversible effect Effects 0.000 claims description 13
- 238000010828 elution Methods 0.000 claims description 4
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 claims description 4
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 229940125773 compound 10 Drugs 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 claims description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 2
- 239000007791 liquid phase Substances 0.000 claims description 2
- 238000004262 preparative liquid chromatography Methods 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 26
- 239000000047 product Substances 0.000 abstract description 18
- 229940079593 drug Drugs 0.000 abstract description 16
- 239000002158 endotoxin Substances 0.000 abstract description 14
- 229920006008 lipopolysaccharide Polymers 0.000 abstract description 14
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 13
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 4
- 235000017709 saponins Nutrition 0.000 description 49
- 235000000346 sugar Nutrition 0.000 description 34
- 230000000694 effects Effects 0.000 description 33
- 210000004027 cell Anatomy 0.000 description 23
- 238000005481 NMR spectroscopy Methods 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- 108090000623 proteins and genes Proteins 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 20
- 239000008280 blood Substances 0.000 description 20
- 210000004369 blood Anatomy 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 19
- 230000001603 reducing effect Effects 0.000 description 18
- 230000002401 inhibitory effect Effects 0.000 description 16
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 15
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 15
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 15
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 14
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 13
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 13
- 206010061218 Inflammation Diseases 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 12
- 108010028144 alpha-Glucosidases Proteins 0.000 description 12
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 12
- 229930193831 cyclocarioside Natural products 0.000 description 11
- 239000000499 gel Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 150000003839 salts Chemical class 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 10
- 150000002772 monosaccharides Chemical group 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- 102000004889 Interleukin-6 Human genes 0.000 description 9
- 108090001005 Interleukin-6 Proteins 0.000 description 9
- 230000036541 health Effects 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 7
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 7
- 102000003945 NF-kappa B Human genes 0.000 description 7
- 108010057466 NF-kappa B Proteins 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 125000000864 peroxy group Chemical group O(O*)* 0.000 description 6
- 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 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000003777 Interleukin-1 beta Human genes 0.000 description 5
- 108090000193 Interleukin-1 beta Proteins 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000001962 electrophoresis Methods 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000002033 PVDF binder Substances 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- 238000004113 cell culture Methods 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 150000002016 disaccharides Chemical class 0.000 description 4
- 239000003292 glue Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000010839 reverse transcription Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108091092584 GDNA Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000006180 TBST buffer Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960002632 acarbose Drugs 0.000 description 3
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 3
- 229960003957 dexamethasone Drugs 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 125000003147 glycosyl group Chemical group 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000002417 nutraceutical Substances 0.000 description 3
- 235000021436 nutraceutical agent Nutrition 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 2
- IFBHRQDFSNCLOZ-IIRVCBMXSA-N 4-nitrophenyl-α-d-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-IIRVCBMXSA-N 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 150000001350 alkyl halides Chemical group 0.000 description 2
- 125000003525 allosyl group Chemical group 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
- 125000000089 arabinosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)CO1)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 125000000600 disaccharide group Chemical group 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000004209 hair Anatomy 0.000 description 2
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 2
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 125000003796 lyxosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000003537 radioprotector Effects 0.000 description 2
- 238000001896 rotating frame Overhauser effect spectroscopy Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000000969 xylosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 description 2
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 1
- 125000006034 1,2-dimethyl-1-propenyl group Chemical group 0.000 description 1
- 125000006035 1,2-dimethyl-2-propenyl group Chemical group 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- 125000005923 1,2-dimethylpropyloxy group Chemical group 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000006080 1-ethyl-1-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000006075 1-ethyl-3-butenyl group Chemical group 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 0.000 description 1
- 125000006025 1-methyl-1-butenyl group Chemical group 0.000 description 1
- 125000006044 1-methyl-1-pentenyl group Chemical group 0.000 description 1
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 description 1
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 description 1
- 125000006055 1-methyl-4-pentenyl group Chemical group 0.000 description 1
- 125000006023 1-pentenyl group Chemical group 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004869 2,2-dimethylpropylcarbonyl group Chemical group CC(CC(=O)*)(C)C 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000004680 2-methylbutylcarbonyl group Chemical group CC(CC(=O)*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 235000021513 Cinchona Nutrition 0.000 description 1
- 241000157855 Cinchona Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- AVGPOAXYRRIZMM-UHFFFAOYSA-N D-Apiose Natural products OCC(O)(CO)C(O)C=O AVGPOAXYRRIZMM-UHFFFAOYSA-N 0.000 description 1
- RFSUNEUAIZKAJO-VRPWFDPXSA-N D-Fructose Natural products OC[C@H]1OC(O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-VRPWFDPXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
- ASNHGEVAWNWCRQ-LJJLCWGRSA-N D-apiofuranose Chemical compound OC[C@@]1(O)COC(O)[C@@H]1O ASNHGEVAWNWCRQ-LJJLCWGRSA-N 0.000 description 1
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N D-apiofuranose Natural products OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000758791 Juglandaceae Species 0.000 description 1
- 208000007976 Ketosis Diseases 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- YQYBUJYBXOVWQW-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1CC2=CC=CC=C2CC1 YQYBUJYBXOVWQW-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000012197 amplification kit Methods 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000006328 iso-butylcarbonyl group Chemical group [H]C([H])([H])C([H])(C(*)=O)C([H])([H])[H] 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004676 n-butylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 210000000282 nail Anatomy 0.000 description 1
- 230000018791 negative regulation of catalytic activity Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- 235000009048 phenolic acids Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 238000002495 two-dimensional nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- DFKDOZMCHOGOBR-UHFFFAOYSA-N zaragozic acid A Natural products O1C(C(O)(C(O2)C(O)=O)C(O)=O)(C(O)=O)C(OC(=O)C=CC(C)CC(C)CC)C(O)C21CCC(=C)C(OC(C)=O)C(C)CC1=CC=CC=C1 DFKDOZMCHOGOBR-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J17/005—Glycosides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Botany (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用。达玛烷型皂苷制采用如下操作步骤制备:S1:取10kg干燥的青钱柳叶,加入75%乙醇水溶液,依次加热回流提取3次,时间为3小时、2小时、2小时,合并滤液,减压回收乙醇,得浸膏2.10kg;S2:取浸膏1.5kg悬浮于20L水中,经D101大孔吸附树脂色谱柱吸附,用水清洗,然后用30%、95%乙醇洗脱,分别得到30%、95%乙醇洗脱物250g、625.0g,该洗脱物作为富含达玛烷型三萜皂苷的青钱柳叶提取物。本发明提供的大部分达玛烷型三萜皂苷化合物均能抑制α‑糖苷酶和抑制脂多糖诱导的RAW264.7细胞中一氧化氮的释放,显示良好的降糖和抗炎活性,且具有浓度依赖性,可用于开发降糖和抗炎的相关药物和保健品。
Description
技术领域
本发明属于生物医药技术领域,具体涉及一种达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用。
背景技术
研究表明,2型糖尿病与细胞因子介导的炎症反应有关,是一种先天的免疫性疾病,炎症在2型糖尿病的发病机制中起媒介作用,此观点被称之为糖尿病“炎症学说”。2005年在美国糖尿病协会会议上,此学说得到了广泛认可,“炎症与2型糖尿病”的关系已成为全球内分泌学者共同关注的热点。
2型糖尿病发病时,病人体内NO、iNOS﹑NF-κB﹑COX-2﹑IL-6﹑IL-1β﹑TNF-α的内源性mRNA的水平显著升高,降糖药物不仅降低病人体内血糖水平,也抑制病人体内NO、TNF-α、IL-6和NF-κB/p65表达,有试验证明抗炎治疗可明显改善2型糖尿病患者糖代谢的异常。
青钱柳为胡桃科青钱柳属植物,为我国特有的植物,是常用药食两用植物,产于江西、广西、贵州、湖南、湖北等南方省。青钱柳性味辛、微苦、平,具有祛风止痒,抗炎降糖的功效,用药历史悠久。
青钱柳的主要化学成分包括达玛烷型皂苷、黄酮类、酚酸类,其中达玛烷型三萜是青钱柳的指标和活性成分。现代药理学研究表明,青钱柳粗提物具有降血糖、抗炎、降血压、降血脂、抗肿瘤、抗氧化、抑菌等作用。
青钱柳叶具有降血糖、抗炎的功效,但其中的降血糖、抗炎物质基础不清,作用机制不明,阻碍了青钱柳叶的深入利用开发。青钱柳叶提取物具有显著的抗炎和降血糖作用,在LPS活化巨噬细胞体外炎症模型上,发现青钱柳叶提取物抗炎效果显著。在四氧嘧啶小鼠糖尿病模型上,发现青钱柳醇提取物具有降血糖作用,其降血糖作用可能与恢复受损的胰岛结构和功能及影响糖的代谢有关;很多研究也都发现水提物、醇提取物都具有降糖作用。临床研究发现,青钱柳制剂降血糖作用显著,而对正常血糖无影响,无毒副作用,与降糖药物有协同作用,对消除糖尿病症状,防治并发症和降糖药毒副作用有较好效果。日本学者发现青钱柳提取物体外可抑制α-葡萄糖苷酶的活性,推测青钱柳可能是通过抑制葡萄糖的吸收而降低血糖,体内可以降低口服蔗糖和淀粉的小鼠血糖水平,在遗传高血糖模型小鼠KK-A上也可显著降低血糖。但是,关于青钱柳中单体化合物降血糖、抗炎的活性研究报道很少。
从青钱柳中得到的达玛烷型皂苷具有抑制α-糖苷酶的活性,抑制炎症细胞中NO的产生,降低iNOS﹑NF-κB﹑COX-2﹑IL-6﹑IL-1β﹑TNF-α的内源性mRNA水平的释放,阻止iNOS、COX-2和NF-κB/p65蛋白的表达,显示良好的降糖和抗炎活性,可用于开发降糖和抗炎的相关药物、保健品。
发明内容
本发明的目的在于通过多种提取、分离手段,从青钱柳叶中提取、分离并鉴定具有降糖和抗炎作用的活性单体化合物,及其在制备降糖和抗炎药物、保健品中的应用。
本发明的目的是通过如下的技术方案实现的:利用多种提取、分离手段,包括溶剂提取法、溶剂萃取法、大孔吸附树脂法、正反硅胶柱层析、凝胶柱层析和制备HPLC等方法,系统研究了青钱柳叶的化学成分。
为实现上述目的,本发明提供如下技术方案:一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包括通式(I)所示的达玛烷型三萜皂苷或其可药用的盐:
通式(I)中,R1、R2、R3各自独立地表示氢原子、卤素原子、C1~C6烷基、C1~C6卤代烷基、C1~C6烷氧基、C1~C6卤代烷氧基、C3~C6环烷基、羟基、氨基、C2~C6烯基、C2~C6炔基、C1~C6烷基羰基、醛基C1~C6烷基、羧基C1~C6烷基、或过氧基;
R4、R5及R6各自独立地表示氢原子、C1~C6烷基、C1~C6卤代烷基、C3~C6环烷基、C2~C6烯基、C2~C6炔基、或糖基。
一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包括通式(Ⅱ)所示的青钱柳中的达玛烷型三萜皂苷或其可药用的盐:
通式(Ⅱ)中,R1、R2各自独立地表示氢原子、卤素原子、C1~C6烷基、C1~C6卤代烷基、C1~C6烷氧基、C1~C6卤代烷氧基、C3~C6环烷基、羟基、氨基、C2~C6烯基、C2~C6炔基、C1~C6烷基羰基、醛基C1~C6烷基、羧基C1~C6烷基、或过氧基;
R3、R4及R5各自独立地表示氢原子、C1~C6烷基、C1~C6卤代烷基、C3~C6环烷基、C2~C6烯基、C2~C6炔基、或糖基。
一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包括通式(Ⅲ)所示的青钱柳中的达玛烷型三萜皂苷或其可药用的盐:
通式(Ⅲ)中,R1表示氢原子、卤素原子、C1~C6烷基、C1~C6卤代烷基、C1~C6烷氧基、C1~C6卤代烷氧基、C3~C6环烷基、羟基、氨基、C2~C6烯基、C2~C6炔基、C1~C6烷基羰基、醛基C1~C6烷基、羧基C1~C6烷基、或过氧基;
R2、R3、R4及R5各自独立地表示氢原子、C1~C6烷基、C1~C6卤代烷基、C3~C6环烷基、C2~C6烯基、C2~C6炔基、或糖基。
优选的,所述糖基包括单糖基或二糖基。
优选的,所述单糖基选自由阿拉伯糖基、核糖基、木糖基、来苏糖基、葡萄糖基、阿洛糖基、甘露糖基、鼠李糖基、鸡纳糖基、果糖基、半乳糖基、芹糖基、葡萄糖醛酸基、半乳糖醛酸基所组成的组中的至少一者;所述二糖基选自由乳糖基、蔗糖基和麦芽糖基所组成的组中的至少一者。
优选的,该达玛烷型三萜皂苷为下述结构式1至结构式2所示的化合物中的任意一者:
[结构式1]为(3α,11α,20S,24R)-四羟基达玛-11-O-β-D-吡喃鸡纳糖苷(青钱柳叶皂苷Z9)。
[结构式2]为(3α,11α,20S,24R,25)-五羟基达玛-3-O-(5'-O-乙酰)-α-L-呋喃阿拉伯糖基-11-O-β-D-吡喃鸡纳糖苷(青钱柳叶皂苷Z10)。
优选的,该达玛烷型三萜皂苷为下述结构式3至结构式7所示的化合物中的任意一者:
[结构式3]为(3α,11α,20S)-三羟基-23R-甲氧基达玛-3-O-α-L-呋喃阿拉伯糖基-11-O-β-D-吡喃鸡纳糖苷(青钱柳叶皂苷Z13)。
[结构式4]为(3α,11α,20S)-三羟基-23R-甲氧基达玛-24-烯-3-O-α-L-呋喃阿拉伯糖基-11-O-α-L-吡喃阿拉伯糖苷(青钱柳叶皂苷Z14)。[结构式5]为(3α,11α,20S)-三羟基-25-甲氧基达玛-23-烯-3-O-α-L-呋喃阿拉伯糖基-11-O-β-D-吡喃鸡纳糖苷(青钱柳叶皂苷Z15)。
[结构式6]为(3α,11α,20S)-三羟基-25-甲氧基达玛-23-烯-3-O-α-L-呋喃阿拉伯糖基-11-O-α-L-吡喃阿拉伯糖苷(青钱柳叶皂苷Z16)。
[结构式7]为(3α,11α,20S)-三羟基-25-甲氧基达玛-23-烯-3-O-(5'-O-乙酰)-α-L-呋喃阿拉伯糖基-11-O-α-L-吡喃阿拉伯糖苷(青钱柳叶皂苷Z17)。优选的,该达玛烷型三萜皂苷为下述结构式8至结构式11所示的化合物中的任意一者:
[结构式8]为(3α,11α,20S)-三羟基达玛-23,25-二烯-3-O-α-L-呋喃阿拉伯糖基-11-O-α-L-吡喃葡萄糖苷(青钱柳叶皂苷Z11)。
[结构式9]为(3α,11α,25)-三羟基达玛-(20S,24R)-环氧-3-O-α-L-呋喃阿拉伯糖基-11-O-α-L-吡喃葡萄糖苷(青钱柳叶皂苷Z18)。
[结构式10]为(3α,11α,25)-三羟基达玛-(20S,24R)-环氧-3-O-(5'-O-乙酰)-α-L-呋喃阿拉伯糖基-11-O-α-L-吡喃葡萄糖苷(青钱柳叶皂苷Z19)。[结构式11]为(3α,11α)-二羟基达玛-20-酮-3-O-α-L-呋喃阿拉伯糖基-11-O-β-D-吡喃鸡纳糖苷(青钱柳叶皂苷Z12)。
一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包含治疗有效量的所述的达玛烷型三萜皂苷或其可药用的盐、或药学可接受的赋形剂以及至少一种生理学上可接受的赋形剂。
本发明的技术效果和优点:本发明提供的达玛烷型三萜皂苷,特别是青钱柳叶皂苷Z9、青钱柳叶皂苷Z10、青钱柳叶皂苷Z13、青钱柳叶皂苷Z14、青钱柳叶皂苷Z15、青钱柳叶皂苷Z16、青钱柳叶皂苷Z17、青钱柳叶皂苷Z11、青钱柳叶皂苷Z18、青钱柳叶皂苷Z19和青钱柳叶皂苷Z12这11个化合物中,大部分化合物均能抑制α-糖苷酶和抑制脂多糖诱导的RAW264.7细胞中一氧化氮的释放,降低iNOS﹑NF-κB﹑COX-2﹑IL-6﹑IL-1β﹑TNF-α的内源性mRNA水平的释放,阻止iNOS、COX-2和NF-κB/p65蛋白的表达,显示良好的降糖和抗炎活性,且具有浓度依赖性,可用于开发降糖和抗炎的相关药物、保健品。
附图说明
图1为本发明的化合物1和2的反应时间-酶活性曲线图;
图2为本发明的化合物2对iNOS、COX-2和NF-κB/p65蛋白的表达影响图;
图3为本发明的化合物2抑制iNOS、COX-2和NF-κB/p65蛋白表达结果图。
具体实施方式
下面将结合本发明实施例,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包括通式(I)所示的达玛烷型三萜皂苷或其可药用的盐:
通式(I)中,R1、R2、R3各自独立地表示氢原子、卤素原子、C1~C6烷基、C1~C6卤代烷基、C1~C6烷氧基、C1~C6卤代烷氧基、C3~C6环烷基、羟基、氨基、C2~C6烯基、C2~C6炔基、C1~C6烷基羰基、醛基C1~C6烷基、羧基C1~C6烷基、或过氧基;
R4、R5及R6各自独立地表示氢原子、C1~C6烷基、C1~C6卤代烷基、C3~C6环烷基、C2~C6烯基、C2~C6炔基、或糖基。
该达玛烷型三萜皂苷为下述结构式1至结构式2所示的化合物中的任意一者:
一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包括通式(Ⅱ)所示的青钱柳中的达玛烷型三萜皂苷或其可药用的盐:
通式(Ⅱ)中,R1、R2各自独立地表示氢原子、卤素原子、C1~C6烷基、C1~C6卤代烷基、C1~C6烷氧基、C1~C6卤代烷氧基、C3~C6环烷基、羟基、氨基、C2~C6烯基、C2~C6炔基、C1~C6烷基羰基、醛基C1~C6烷基、羧基C1~C6烷基、或过氧基;
R3、R4及R5各自独立地表示氢原子、C1~C6烷基、C1~C6卤代烷基、C3~C6环烷基、C2~C6烯基、C2~C6炔基、或糖基。
该达玛烷型三萜皂苷为下述结构式3至结构式7所示的化合物中的任意一者:
一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包括通式(Ⅲ)所示的青钱柳中的达玛烷型三萜皂苷或其可药用的盐:
通式(Ⅲ)中,R1表示氢原子、卤素原子、C1~C6烷基、C1~C6卤代烷基、C1~C6烷氧基、C1~C6卤代烷氧基、C3~C6环烷基、羟基、氨基、C2~C6烯基、C2~C6炔基、C1~C6烷基羰基、醛基C1~C6烷基、羧基C1~C6烷基、或过氧基;
R2、R3、R4及R5各自独立地表示氢原子、C1~C6烷基、C1~C6卤代烷基、C3~C6环烷基、C2~C6烯基、C2~C6炔基、或糖基。
该达玛烷型三萜皂苷为下述结构式8至结构式11所示的化合物中的任意一者:
所述糖基包括单糖基或二糖基。
所述单糖基选自由阿拉伯糖基、核糖基、木糖基、来苏糖基、葡萄糖基、阿洛糖基、甘露糖基、鼠李糖基、鸡纳糖基、果糖基、半乳糖基、芹糖基、葡萄糖醛酸基、半乳糖醛酸基所组成的组中的至少一者;所述二糖基选自由乳糖基、蔗糖基和麦芽糖基所组成的组中的至少一者。
一种达玛烷型皂苷在制备降糖和抗炎药物、保健品中的应用,包含治疗有效量的所述的达玛烷型三萜皂苷或其可药用的盐、或药学可接受的赋形剂以及至少一种生理学上可接受的赋形剂。
本发明中,“卤素原子”表示氟原子、氯原子、溴原子、碘原子。
本发明中,“C1~C6”表示后续的取代基的碳原子数为1~6。
本发明中,“C1~C6烷基”表示碳原子数为1~6的直链或支链烷基,例如,可列举甲基、乙基、正丙基、异丙基、正丁基、仲丁基、异丁基、叔丁基、正戊基、新戊基、1-甲基丁基、2-甲基丁基、3-甲基丁基、1-乙基丙基、1,1-二甲基丙基、1,2-二甲基丙基、正己基、1-甲基戊基、2-甲基戊基、3-甲基戊基、4-甲基戊基、1-乙基丁基、2-乙基丁基、1,1-二甲基丁基、1,2-二甲基丁基、1,3-二甲基丁基、2,2-二甲基丁基、2,3-二甲基丁基、3,3-二甲基丁基、1,1,2-三甲基丙基、1,2,2-三甲基丙基、1-乙基-1-甲基丙基或1-乙基-2-甲基丙基等基。
本发明中,“C2~C6烯基”表示碳原子数为2~6的直链或支链烯基,例如,可列举出乙烯基、1-丙烯基、2-丙烯基、1-丁烯基、2-丁烯基、3-丁烯基、2-甲基-1-丙烯基、1,3-丁二烯基、1-戊烯基、2-戊烯基、1-甲基-1-丁烯基、3-戊烯基、1-甲基-2-丁烯基、4-戊烯基、1-甲基-3-丁烯基、1,2-二甲基-2-丙烯基、2-甲基-2-丁烯基、1,2-二甲基-1-丙烯基、1,3-戊二烯基、1-己烯基、2-己烯基、1-甲基-1-戊烯基、3-己烯基、4-己烯基、5-己烯基、1-甲基-4-戊烯基、1-乙基-3-丁烯基、1-(异丁基)乙烯基、1-乙基-1-甲基-2-丙烯基、1-(异丙基)-2-丙烯基、1,3-二甲基-2-丁烯基、3-甲基-4-戊烯基、1,1,2-三甲基-2-丙烯基或1,5-己二烯基等基。
本发明中,“C2~C6炔基”表示碳原子数为2~6的直链或支链炔基,例如,可列举出乙炔基、1-丙炔基、2-丙炔基、1-丁炔基、2-丁炔基、3-丁炔基、1-戊炔基、2-戊炔基、3-戊炔基、1-甲基-2-丁炔基、4-戊炔基、1-甲基-3-丁炔基、1-己炔基、2-己炔基、3-己炔基、1-甲基-2-戊炔基、5-己炔基、1-乙基-3-丁炔基、1-乙基-1-甲基-2-丙炔基、或1,1-二甲基-2-丁炔基等基。
本发明中,“C1~C6卤代烷基”表示被相同或不同的1~6个卤素原子取代的碳原子数为1~6的直链或支链烷基,例如可列举出:氟甲基、二氟甲基、溴甲基、二溴甲基、碘甲基、氯二氟甲基、1-氟乙基、1,1-二氟乙基、2,2,2-三氟乙基、1,1,2,2-四氟乙基、五氟乙基、1-氟丙基、1,1-二氟丙基、3,3,3-三氟丙基、1-溴丙基、1-氟丁基、4,4-二氟丁基、4,4,4-三氟-3-甲基丁基、2,2,3,4,4,4-六氟丁基、1-氯丁基、1-溴丁基、1-碘丁基、1-氟戊基、5,5,5-三氟戊基、1-氯戊基、5,5,5-三氯戊基、1-溴戊基、1-氟己基、6,6,6-三氟己基、1-氯己基或6-碘己基等基。
本发明中,“C1~C6烷氧基”表示烷基部分为上述定义的(C1~C6烷基)-O-基,例如,可列举出甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、1-甲基丁氧基、2-甲基丁氧基、3-甲基丁氧基、1-乙基丙氧基、1,1-二甲基丙氧基、1,2-二甲基丙氧基或正己基氧基等基。
本发明中,“C1~C6卤代烷氧基”表示卤代烷基部分为上述定义的(C1~C6卤代烷)-O-基,例如,可列举出二氟甲氧基、二氯甲氧基、三氟甲氧基、三氯甲氧基、三溴甲氧基、2-氟乙氧基、1-氯乙氧基、1-溴乙氧基、2,2-二氟乙氧基、2,2-二氯乙氧基、2,2,2-三氟乙氧基、2,2,2-三氯乙氧基、1,1,2,2-四氟乙氧基、1-氯丙氧基、2-溴丙氧基、2-溴-1-甲基乙氧基、3-碘丙氧基、2,3-二氯丙氧基、2,3-二溴丙氧基、3,3,3-三氟丙氧基、1-溴-3,3,3-三氟丙氧基、2,2,3,3,3-五氟丙氧基、2,2,2-三氟-1-三氟甲基乙氧基、2-氯丁氧基、4-溴丁氧基、3-溴-2-甲基丙氧基、4,4,4-三氟丁氧基、5,5,5-三氟戊氧基、或4,4,5,5,5-五氟戊氧基等基。
本发明中,“C3~C6环烷基”表示碳原子数为3~6的环烷基,例如,可列举出环丙基、环丁基、环戊基或环己基等基。
本发明中,“C1~C6烷基羰基”表示烷基部分为上述定义的(C1~C6烷基)-C(=O)-基,例如,可列举出甲基羰基、乙基羰基、正丙基羰基、异丙基羰基、正丁基羰基、异丁基羰基、仲丁基羰基、叔丁基羰基、正戊基羰基、2-甲基丁基羰基、2,2-二甲基丙基羰基、或正己基羰基等基。
本发明中,“醛基C1~C6烷基”表示烷基部分为上述定义的H-C(=O)-(C1~C6烷基)-基,例如,可列举出甲醛基、醛基甲基、醛基乙基、醛基正丙基、醛基异丙基、醛基正丁基、醛基异丁基、醛基仲丁基、醛基叔丁基、醛基正戊基、醛基2-甲基丁基、醛基2,2-二甲基丙基、或醛基正己基等基。
本发明中,“羧基C1~C6烷基”表示烷基部分为上述定义的HO-C(=O)-(C
1~C6烷基)-基,例如,可列举出甲羧基、羧基甲基、羧基乙基、羧基正丙基、羧基异丙基、羧基正丁基、羧基异丁基、羧基仲丁基、羧基叔丁基、羧基正戊基、或羧基正己基等基。
本发明中,糖基包括单糖基、或二糖基。
单糖是多羟基醛或酮类化合物,以五碳糖和六碳糖最常见。五碳醛糖包括L-阿拉伯糖、D-木糖、D-来苏糖、D-核糖。六碳醛糖包括D-葡萄糖、D-甘露糖、D-阿洛糖、D-半乳糖。六碳酮糖包括D-果糖、L-山梨糖。其中,优选为D-葡萄糖、D-鸡纳糖、D-木糖、L-阿拉伯糖。
另外,作为单糖分子的一个羟基被氢原子取代的单糖,常见的有6-去氧糖(甲基五碳糖),例如包括D-鸡纳糖、L-鼠李糖。
单糖分子中的伯醇羟基氧化成羧基,从而形成为糖醛酸,例如包括葡萄糖醛酸和半乳糖醛酸。
糖链中含有支链的单糖类称为支碳链糖,例如包括D-芹糖。
二糖又名双糖,由二分子的单糖通过糖苷键形成,例如包括乳糖、蔗糖和麦芽糖。
本发明中,可药用的盐类指的是在通式(I)或(II)所表示的本发明化合物当中,羟基、羧基或氨基等与金属或有机碱形成的盐类、或者与无机酸或有机酸形成的盐类。作为金属,可列举出钠或钾等碱金属或者镁或钙等碱土类金属;作为有机碱,可列举出三乙胺或二异丙胺等;作为无机酸,可列举出磷酸、盐酸、氢氢溴酸、氢碘酸、硼酸或硫酸等;作为有机酸,可列举出甲酸、醋酸、乳酸、抗坏血酸、琥珀酸、富马酸、马来酸、草酸、柠檬酸、苯甲酸、水杨酸、酒石酸、甲磺酸、4-甲苯磺酸或三氟甲磺酸等。
本发明的新达玛烷型三萜皂苷可以从青钱柳叶中分离得到。因此,本发明另一方面还提供一种包含上述达玛烷型三萜皂苷的青钱柳叶提取物。具体来说,将青钱柳叶用含水乙醇溶液回流提取,减压回收溶剂,得到浸膏。将该浸膏悬浮于水中,经大孔吸附树脂色谱柱分离,分别得到水洗脱物、30%乙醇洗脱物、和95%乙醇洗脱物,其中95%乙醇洗脱物为富含上述达玛烷型三萜皂苷的青钱柳叶提取物。
接下来,将95%乙醇洗脱物经硅胶柱层析得到多个流份,分别对各个流份进一步采用正反硅胶柱层析、凝胶柱层析和制备HPLC等方法进行精制,从而获得上述纯的化合物1-11。
可以采用1H-NMR、13C-NMR等一维核磁共振谱以及1H-1HCOSY、DEPT、HSQC、HMBC、ROESY等二维核磁共振谱等波谱技术、HRESIMS质谱和化学反应对上述所得到的化合物1-11的结构进行鉴定。
上述提取、分离、精制、以及结构鉴定过程中的具体操作对于本领域技术人员来说是公知的,可以参考相应的文献、技术手册或教科书中记载的内容来进行。
本发明还提供一种药物、保健品组合物,包含治疗有效量的上述达玛烷型三萜皂苷以及任选的药学可接受的赋形剂。
上述药学可接受的赋形剂可以是药物制剂、保健品领域中任何常规的赋形剂,特定赋形剂的选择将取决于用于治疗特定患者的给药方式或疾病类型和状态,用于特定给药模式的合适药物、保健品组合物的制备方法完全在药物、保健品领域技术人员的知识范围内。例如,可以作为药学可接受的赋形剂包括药学领域常规的稀释剂、载体、填充剂、粘合剂、湿润剂、崩解剂等。
上述药物、保健品组合物可以制成片剂、粉剂、颗粒剂、胶囊、口服液、注射乳剂、注射用无菌粉针等多种形式。上述各种剂型的药物、保健品均可以按照药学领域的常规方法制备。
本发明进一步提供一种化妆品组合物,包含上述达玛烷型三萜皂苷以及任选的至少一种生理学上可接受的赋形剂。术语“生理学上可接受的赋形剂”是指适合于局部或口服使用并且当与哺乳动物(特别是人类)的粘膜、指甲、头皮、头发、体毛和皮肤等接触时不存在任何毒性、不相容性等的风险的物质。根据本发明,生理学上可接受的赋形剂优选是美容上可接受的赋形剂。可适用的这些赋形剂是本领域技术人员熟知的,包括例如润肤剂、有机溶剂、螯合剂、渗透剂、增稠剂、填充剂、乳化剂或表面活性剂、防腐剂、着色剂、芳香剂、和其混合物。
上述化妆品组合物可以呈凝胶、乳液、微乳液、精华、油、面膜、药膏、软膏、化妆水、浓缩液、悬浮液、泡沫、固体棒或气溶胶的形式。
除了上述达玛烷型三萜皂苷以外,根据本发明的化妆品组合物还可以含有一种或多种第二活性剂,所述第二活性剂能够增强上述达玛烷型三萜皂苷的活性并且与其相容,即不易相互反应或者掩盖或限制其作用。特别地,第二活性剂可以例如选自保湿剂、湿润剂、抗氧化剂、皮肤保护剂、抗老化活性剂、防射线剂特别是防UV射线剂、及其混合物。
实施例1
一种达玛烷型皂苷制备方法,包括如下操作步骤:
S1:取10kg干燥的青钱柳叶,加入75%乙醇水溶液,依次加热回流提取3次,时间为3小时、2小时、2小时,合并滤液,减压回收乙醇,得浸膏2.10kg;
S2:取浸膏1.5kg悬浮于20L水中,经D101大孔吸附树脂色谱柱吸附,用水清洗,然后用30%、95%乙醇洗脱,分别得到30%、95%乙醇洗脱物250g、625.0g,该洗脱物作为富含达玛烷型三萜皂苷的青钱柳叶提取物。
实施例2
达玛烷型三萜皂苷化合物1-11的分离制备及结构鉴定。
化合物1-11分离是同时进行的,因而在一个实施例中进行描述。
[化合物1-11的分离制备]
取上述实施例1中所获得的95%乙醇洗脱物150.0g,经硅胶柱层析,以二氯甲烷-甲醇(100:0、60:1、20:1、10:1、8:1、4:1、2:1、0:100)为洗脱剂进行梯度洗脱,得到Fr.A(22g)、Fr.B(16g)、Fr.C(23g)、Fr.D(15g)、Fr.E(27g)、Fr.F(19g)、Fr.G(13g)和Fr.H(6g)。将组分Fr.F(19g)经过反相C18硅胶柱层析,以水-甲醇(100:0-0:100)为洗脱剂进行梯度洗脱,得到6个组分为Fr.F.1(0.5g)、Fr.F.2(3.5g)、Fr.F.3(4.2g)、Fr.F.4(2.5g)、Fr.F.5(1.5g)和Fr.F.6(1.1g)。将组分Fr.F.3(4.2g)经过反相C18硅胶柱层析(MeOH-H2O,60:40→100:0),得到Fr.F.3.1(300mg)、Fr.F.3.2(1315mg)、Fr.F.3.3(345mg)、Fr.F.3.4(870mg)、Fr.F.3.5(460mg)和Fr.F.3.6(234mg)。Fr.F.3.2(1315mg)经过反相C18硅胶柱层析制备色谱、半制备液相色谱(50%乙腈),得到化合物2(10.7mg)、11(6.2mg)和9(7.1mg);将组分Fr.F.3.3(345mg)经过葡聚糖凝胶Sephadex LH-20、反相C18硅胶柱层析及半制备液相纯化(50%乙腈),得到化合物3(6.2mg)、4(5.0mg)和5(4.7mg)和10(7.5mg);将组分Fr.F.3.4(870mg)经过制备、半制备反相C18硅胶柱层析(78%甲醇),得到化合物6(4.1mg)和7(6.6mg);将组分Fr.F.3.5经过反相C18硅胶柱层析,葡聚糖凝胶Sephadex LH-20/半制备反相C18硅胶柱层析(50%乙腈),得到化合物1(14.3mg)和8(7.4mg)。
[结构鉴定]
主要利用包括红外、质谱、核磁共振谱(1HNMR、13CNMR、DEPT、1H-1HCOSY、HSQC、HMBC、ROESY)、质谱(MS)和旋光度等光谱技术,,鉴定上述所得到的化合物1-11的结构。
运用二维核磁共振谱波谱技术,确定了取代基的位置和糖的连接位置,结合高分辨质谱,对它们的全部碳信号和氢信号进行了确切的归属。化合物1-11的理化数据如下所示。
化合物1:青钱柳叶皂苷Z9(cyclocarioside Z9)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+645.4342(calculated for C36H62O8Na,found:645.4341);1H NMR(600MHz,pyridine-d5)δH 3.08(1H,m,H-1a),δH 2.12(1H,m,H-1b),δH 2.16(1H,m,H-2a),δH 1.75(1H,m,H-2b),δH 3.62(1H,m,H-3),δH 1.80(1H,m,H-5),δH 1.54(1H,m,H-6a),δH 1.47(1H,m,H-6b),δH1.63(1H,m,H-7a),δH 1.22(1H,m,H-7b),δH 2.04(1H,m,H-9),δH 4.48(1H,m,H-11),δH2.95(1H,m,H-12a),δH1.71(1H,m,H-12b),δH 2.16(1H,m,H-13),δH 1.53(1H,m,H-15a),δH1.06(1H,m,H-15b),δH 2.14(1H,m,H-16a),δH 1.74(1H,m,H-16b),δH 1.80(1H,m,H-17),δH1.11(3H,s,H-18),δH 1.40(3H,s,H-19),δH 1.44(3H,s,H-21),δH 2.12(1H,m,H-22a),δH1.96(1H,m,H-22b),δH 2.10(1H,m,H-23a),δH 2.02(1H,dt,H-23b),δH 4.42(1H,s,H-24),δH 5.30(1H,s,H-26a),δH 4.98(1H,s,H-26b),δH 1.91(3H,s,H-27),δH 1.00(3H,s,H-28),δH 1.26(3H,s,H-29),δH 0.87(3H,s,H-30),δH 4.93(1H,d,H-1″),δH 3.98(1H,d,H-2″),δH4.10(1H,m,H-3″),δH 3.66(1H,dd,H-4″),δH 3.60(1H,t,H-5″),δH 1.61(1H,d,H-6″);13CNMR(150MHz,pyridine-d5)δC35.9(C-1),δC 26.1(C-2),δC 75.7(C-3),δC 39.1(C-4),δC51.2(C-5),δC 18.9(C-6),δC 37.0(C-7),δC 50.6(C-8),δC 54.8(C-9),δC 40.6(C-10),δC77.0(C-11),δC 35.3(C-12),δC 42.0(C-13),δC 41.1(C-14),δC 31.9(C-15),δC 27.5(C-16),δC 50.5(C-17),δC 17.7(C-18),δC 17.3(C-19),δC 74.4(C-20),δC 27.2(C-21),δC38.2(C-22),δC 31.0(C-23),δC 76.3(C-24),δC 150.3(C-25),δC 110.6(C-26),δC 19.0(C-27),δC 23.4(C-28),δC 30.5(C-29),δC 17.2(C-30),δC 102.1(C-1″),δC 76.2(C-2″),δC78.7(C-3″),δC 77.3(C-4″),δC 73.2(C-5″),δC 19.1(C-6″)。
化合物2:青钱柳叶皂苷Z10(cyclocarioside Z10)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M-H]-813.5000(calculated for C43H73O14,found:813.4999);1H NMR(500MHz,pyridine-d5)δH 2.99(1H,m,H-1a),δH 1.80(1H,m,H-1b),δH 1.79(1H,m,H-2a),δH 1.65(1H,m,H-2b),δH 3.54(1H,t,H-3),δH 1.54(1H,m,H-5),δH 1.53(1H,m,H-6a),δH 1.47(1H,m,H-6b),δH1.53(1H,m,H-7a),δH 1.19(1H,m,H-7b),δH 1.88(1H,m,H-9),δH 4.45(1H,m,H-11),δH2.97(1H,m,H-12a),δH 1.59(1H,m,H-12b),δH 2.02(1H,m,H-13),δH 1.42(1H,m,H-15a),δH1.01(1H,m,H-15b),δH 1.75(1H,m,H-16a),δH 1.44(1H,m,H-16b),δH 1.89(1H,m,H-17),δH1.08(3H,s,H-18),δH 1.33(3H,s,H-19),δH 1.25(3H,s,H-21),δH 2.29(1H,m,H-22a),δH1.75(1H,m,H-22b),δH 1.90(1H,m,H-23a),δH 1.78(1H,m,H-23b),δH 3.68(1H,d,H-24),δH1.50(3H,s,H-26),δH 1.29(3H,s,H-27),δH 0.93(3H,s,H-28),δH 1.24(3H,s,H-29),δH0.76(3H,s,H-30),δH 1.96(3H,s,CH3COO-),δH 5.49(1H,m,H-1′),δH 4.84(1H,d,H-2′,J=2.8),δH 4.61(1H,m,H-3′,J=3.4),δH 4.72(1H,td,H-4′,J=6.9),δH 4.79(1H,dd,H-5a′,J=11.6),δH 4.59(1H,m,H-5b′),δH 5.03(1H,d,H-1″,J=7.7),δH 3.94(1H,t,H-2″,J=8.4),δH 4.13(1H,t,H-3″,J=8.8),δH 3.68(1H,t,H-4″,J=8.9),δH 3.74(1H,m,H-5″),δH1.55(1H,t,H-6″,J=5.9);13C NMR(125MHz,pyridine-d5)δC 36.0(C-1),δC 21.7(C-2),δC79.9(C-3),δC 38.2(C-4),δC 51.5(C-5),δC 18.6(C-6),δC 36.7(C-7),δC 50.8(C-8),δC54.4(C-9),δC 40.3(C-10),δC 77.3(C-11),δC 34.9(C-12),δC 41.8(C-13),δC 40.9(C-14),δC 31.8(C-15),δC 26.1(C-16),δC 51.3(C-17),δC 17.4(C-18),δC 17.3(C-19),δC76.3(C-20),δC 27.0(C-21),δC 27.0(C-22),δC 24.8(C-23),δC 70.3(C-24),δC 75.0(C-25),δC 27.7(C-26),δC 29.2(C-27),δC 23.2(C-28),δC 29.2(C-29),δC 17.0(C-30),δC171.1(CH3COO-),δC 21.0(CH3COO-),δC 106.8(C-1′),δC 84.4(C-2′),δC 80.1(C-3′),δC81.8(C-4′),δC 65.4(C-5′),δC 101.7(C-1″),δC 75.8(C-2″),δC 78.7(C-3″),δC 77.2(C-4″),δC 73.1(C-5″),δC 18.9(C-6″)。
化合物3:青钱柳叶皂苷Z13(cyclocarioside Z13)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+791.4921(calculated for C42H72O12Na,found:791.4924);1H NMR(500MHz,pyridine-d5)δH 3.02(1H,m,H-1a),δH 1.83(1H,m,H-1b),δH 1.81(1H,m,H-2a),δH 1.70(1H,m,H-2b),δH 3.60(1H,m,H-3),δH 1.56(1H,m,H-5),δH 1.48(1H,m,H-6a),δH 1.45(1H,m,H-6b),δH1.54(1H,m,H-7a),δH 1.18(1H,m,H-7b),δH 1.90(1H,m,H-9),δH 4.47(1H,m,H-11),δH2.99(1H,m,H-12a),δH 1.67(1H,m,H-12b),δH 2.12(1H,m,H-13),δH 1.48(1H,m,H-15a),δH1.03(1H,m,H-15b),δH 1.75(1H,m,H-16a),δH 1.45(1H,m,H-16b),δH 1.85(1H,m,H-17),δH1.07(3H,s,H-18),δH 1.35(3H,s,H-19),δH 1.43(3H,s,H-21),δH 2.14(1H,m,H-22a),δH1.67(1H,m,H-22b),δH 4.39(1H,m,H-23),δH 5.15(1H,dt,H-24),δH 1.69(3H,s,H-26),δH1.68(3H,s,H-27),δH 0.95(3H,s,H-28),δH 1.28(3H,s,H-29),δH 0.79(3H,s,H-30),δH3.19(3H,s,-OCH3),δH 5.54(1H,br s,H-1′),δH 4.86(1H,m,H-2′),δH 4.82(1H,m,H-3′),δH4.72(1H,td,H-4′,J=3.4),δH 4.36(1H,dd,H-5a′),δH 4.26(1H,m,H-5b′),δH 4.95(1H,d,H-1″,J=7.7),δH 3.95(1H,d,H-2″),δH 4.09(1H,m,H-3″,J=8.8),δH 3.66(1H,dd,H-4″),δH 3.63(1H,t,H-5″),δH 1.60(3H,d,H-6″);13C NMR(125MHz,pyridine-d5)δC 36.0(C-1),δC 21.7(C-2),δC 79.6(C-3),δC 38.3(C-4),δC 51.5(C-5),δC 18.7(C-6),δC 36.7(C-7),δC 51.3(C-8),δC 54.4(C-9),δC 40.3(C-10),δC 76.8(C-11),δC 35.1(C-12),δC 41.8(C-13),δC 40.8(C-14),δC 31.6(C-15),δC 26.0(C-16),δC 50.8(C-17),δC 17.5(C-18),δC17.0(C-19),δC 74.6(C-20),δC 27.8(C-21),δC 45.1(C-22),δC 76.1(C-23),δC 127.3(C-24),δC 135.8(C-25),δC 18.5(C-26),δC 26.1(C-27),δC 23.3(C-28),δC 30.3(C-29),δC17.0(C-30),δC 106.8(C-1′),δC 84.4(C-2′),δC 79.8(C-3′),δC 86.0(C-4′),δC 63.3(C-5′),δC 101.8(C-1″),δC 75.9(C-2″),δC 78.6(C-3″),δC 77.2(C-4″),δC 73.0(C-5″),δC18.9(C-6″),δC 55.5(-OCH3)。
化合物4:青钱柳叶皂苷Z14(cyclocarioside Z14)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+777.4765(calculated for C41H70O12Na,found:777.4768);1H NMR(500MHz,pyridine-d5)δH 3.06(1H,m,H-1a),δH 1.83(1H,m,H-1b),δH 1.73(1H,m,H-2a),δH 1.61(1H,m,H-2b),δH 3.55(1H,m,H-3),δH 1.55(1H,m,H-5),δH 1.48(1H,m,H-6a),δH 1.45(1H,m,H-6b),δH1.53(1H,m,H-7a),δH 1.16(1H,m,H-7b),δH 1.90(1H,m,H-9),δH 4.48(1H,m,H-11),δH3.04(1H,m,H-12a),δH 1.66(1H,m,H-12b),δH 2.12(1H,m,H-13),δH 1.48(1H,m,H-15a),δH1.04(1H,m,H-15b),δH 1.73(1H,m,H-16a),δH 1.45(1H,m,H-16b),δH 1.86(1H,m,H-17),δH1.03(3H,s,H-18),δH 1.32(3H,s,H-19),δH 1.47(3H,s,H-21),δH 2.18(1H,m,H-22a),δH1.66(1H,m,H-22b),δH 4.42(1H,m,H-23),δH 5.21(1H,dt,H-24),δH 1.72(3H,s,H-26),δH1.71(3H,s,H-27),δH 0.91(3H,s,H-28),δH 1.25(3H,s,H-29),δH 0.77(3H,s,H-30),δH3.21(3H,s,-OCH3),δH 5.49(1H,br s,H-1′),δH 4.84(1H,m,H-2′),δH 4.83(1H,m,H-3′),δH4.71(1H,td,H-4′,J=3.4),δH 4.35(1H,dd,H-5a′),δH 4.26(1H,m,H-5b′),δH 4.81(1H,d,H-1″,J=3.9),δH 4.34(1H,d,H-2″,J=7.4),δH 4.05(1H,m,H-3″,J=9.2),δH 4.20(1H,dd,H-4″),δH 4.28(1H,t,H-5a″),δH 3.62(3H,d,H-5b″);13C NMR(125MHz,pyridine-d5)δC36.0(C-1),δC 21.6(C-2),δC 79.6(C-3),δC 38.3(C-4),δC 51.6(C-5),δC 18.7(C-6),δC36.6(C-7),δC 51.3(C-8),δC 54.4(C-9),δC 40.3(C-10),δC 76.9(C-11),δC 34.9(C-12),δC 41.8(C-13),δC 40.7(C-14),δC 31.6(C-15),δC 26.0(C-16),δC 50.7(C-17),δC 17.5(C-18),δC 17.2(C-19),δC 74.6(C-20),δC 27.9(C-21),δC 45.0(C-22),δC 76.1(C-23),δC127.4(C-24),δC 135.8(C-25),δC 18.6(C-26),δC 26.1(C-27),δC 30.3(C-28),δC 23.3(C-29),δC 17.0(C-30),δC 106.7(C-1′),δC 84.3(C-2′),δC 79.8(C-3′),δC 86.0(C-4′),δC63.3(C-5′),δC 102.8(C-1″),δC 73.1(C-2″),δC 75.1(C-3″),δC 70.1(C-4″),δC 67.9(C-5″),δC 55.5(-OCH3)。
化合物5:青钱柳叶皂苷Z15(cyclocarioside Z15)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+791.4921(calculated for C42H72O12Na,found:791.4917);1H NMR(600MHz,pyridine-d5)δH 3.03(1H,m,H-1a),δH 1.84(1H,m,H-1b),δH 1.83(1H,m,H-2a),δH 1.70(1H,m,H-2b),δH 3.61(1H,m,H-3),δH 1.56(1H,m,H-5),δH 1.50(1H,m,H-6a),δH 1.47(1H,m,H-6b),δH 1.58(1H,m,H-7a),δH 1.20(1H,m,H-7b),δH 1.90(1H,m,H-9),δH 4.47(1H,m,H-11),δH 2.98(1H,m,H-12a),δH 1.69(1H,m,H-12b),δH 2.18(1H,m,H-13),δH 1.55(1H,m,H-15a),δH 1.07(1H,m,H-15b),δH 1.92(1H,m,H-16a),δH 1.84(1H,m,H-16b),δH 1.96(1H,m,H-17),δH 1.09(3H,s,H-18),δH 1.35(3H,s,H-19),δH 1.44(3H,s,H-21),δH 2.61(1H,m,H-22a),δH 2.43(1H,m,H-22b),δH 5.98(1H,m,H-23),δH 5.65(1H,dt,H-24),δH 1.31(3H,s,H-26),δH 1.31(3H,s,H-27),δH 0.96(3H,s,H-28),δH 1.29(3H,s,H-29),δH 0.80(3H,s,H-30),δH 3.20(3H,s,-OCH3),δH 5.51(1H,br s,H-1′),δH 4.88(1H,m,H-2′),δH 4.84(1H,m,H-3′),δH 4.75(1H,td,H-4′,J=3.4),δH 4.38(1H,dd,H-5a′),δH 4.28(1H,m,H-5b′),δH4.94(1H,d,H-1″,J=7.7),δH 3.96(1H,d,H-2″,J=8.3),δH 4.11(1H,m,H-3″,J=8.8),δH3.69(1H,dd,H-4″),δH 3.64(1H,t,H-5a″),δH 1.62(3H,d,H-6″);13C NMR(150MHz,pyridine-d5)δC 35.9(C-1),δC 21.6(C-2),δC 79.6(C-3),δC 38.3(C-4),δC 51.3(C-5),δC18.7(C-6),δC 36.7(C-7),δC 50.9(C-8),δC 54.3(C-9),δC 40.3(C-10),δC 76.8(C-11),δC35.1(C-12),δC 41.8(C-13),δC 40.9(C-14),δC 31.6(C-15),δC 25.8(C-16),δC 50.7(C-17),δC 17.5(C-18),δC 17.0(C-19),δC 74.4(C-20),δC 27.9(C-21),δC 44.8(C-22),δC127.8(C-23),δC 138.6(C-24),δC 75.3(C-25),δC 26.2(C-26),δC 26.9(C-27),δC 23.3(C-28),δC 30.3(C-29),δC 16.9(C-30),δC 106.7(C-1′),δC 84.4(C-2′),δC 79.7(C-3′),δC86.0(C-4′),δC 63.3(C-5′),δC 101.9(C-1″),δC 75.9(C-2″),δC 78.6(C-3″),δC 77.2(C-4″),δC 73.0(C-5″),δC 19.0(C-6″),δC 50.5(-OCH3)。
化合物6:青钱柳叶皂苷Z16(cyclocarioside Z16)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+777.4765(calculated for C41H70O12Na,found:777.4769);1H NMR(600MHz,pyridine-d5)δH 3.07(1H,m,H-1a),δH 1.83(1H,m,H-1b),δH 1.82(1H,m,H-2a),δH 1.70(1H,m,H-2b),δH 3.55(1H,m,H-3),δH 1.54(1H,m,H-5),δH 1.51(1H,m,H-6a),δH 1.44(1H,m,H-6b),δH 1.55(1H,m,H-7a),δH 1.18(1H,m,H-7b),δH 1.90(1H,m,H-9),δH 4.47(1H,m,H-11),δH 3.02(1H,m,H-12a),δH 1.67(1H,m,H-12b),δH 2.17(1H,m,H-13),δH 1.53(1H,m,H-15a),δH 1.08(1H,m,H-15b),δH 1.90(1H,m,H-16a),δH 1.83(1H,m,H-16b),δH 1.96(1H,m,H-17),δH 1.05(3H,s,H-18),δH 1.32(3H,s,H-19),δH 1.47(3H,s,H-21),δH 2.62(1H,m,H-22a),δH 2.46(1H,m,H-22b),δH 6.00(1H,m,H-23),δH 5.67(1H,dt,H-24),δH 1.31(3H,s,H-26),δH 1.31(3H,s,H-27),δH 0.90(3H,s,H-28),δH 1.26(3H,s,H-29),δH 0.78(3H,s,H-30),δH 3.21(3H,s,-OCH3),δH 5.48(1H,br s,H-1′),δH 4.84(1H,m,H-2′),δH 4.81(1H,m,H-3′),δH 4.72(1H,td,H-4′,J=3.4),δH 4.34(1H,dd,H-5a′),δH 4.27(1H,m,H-5b′),δH4.83(1H,d,H-1″),δH 4.36(1H,d,H-2″),δH 4.06(1H,m,H-3″,J=9.2),δH 4.21(1H,dd,H-4″),δH 4.30(1H,t,H-5a″),δH 3.64(1H,d,H-5b″);13C NMR(150MHz,pyridine-d5)δC 36.0(C-1),δC 21.6(C-2),δC 79.6(C-3),δC 38.3(C-4),δC 51.3(C-5),δC 18.6(C-6),δC 36.7(C-7),δC 50.9(C-8),δC 54.3(C-9),δC 40.3(C-10),δC 77.0(C-11),δC 34.9(C-12),δC41.8(C-13),δC 41.0(C-14),δC 31.6(C-15),δC 25.9(C-16),δC 50.8(C-17),δC 17.5(C-18),δC 17.2(C-19),δC 74.5(C-20),δC 27.8(C-21),δC 44.7(C-22),δC 127.4(C-23),δC138.6(C-24),δC 75.3(C-25),δC 26.3(C-26),δC 26.9(C-27),δC 23.3(C-28),δC 30.3(C-29),δC 17.1(C-30),δC 106.7(C-1′),δC 84.3(C-2′),δC 79.8(C-3′),δC 86.1(C-4′),δC63.3(C-5′),δC 102.8(C-1″),δC 73.0(C-2″),δC 75.1(C-3″),δC 70.1(C-4″),δC 67.9(C-5″),δC 50.5(-OCH3)。
化合物7:青钱柳叶皂苷Z17(cyclocarioside Z17)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+833.5027(calculated for C44H74O13Na,found:833.5028);1H NMR(600MHz,pyridine-d5)δH 3.07(1H,m,H-1a),δH 1.83(1H,m,H-1b),δH 1.82(1H,m,H-2a),δH 1.70(1H,m,H-2b),δH 3.55(1H,m,H-3),δH 1.54(1H,m,H-5),δH 1.51(1H,m,H-6a),δH 1.44(1H,m,H-6b),δH 1.55(1H,m,H-7a),δH 1.18(1H,m,H-7b),δH 1.90(1H,m,H-9),δH 4.47(1H,m,H-11),δH 3.02(1H,m,H-12a),δH 1.67(1H,m,H-12b),δH 2.17(1H,m,H-13),δH 1.53(1H,m,H-15a),δH 1.08(1H,m,H-15b),δH 1.90(1H,m,H-16a),δH 1.83(1H,m,H-16b),δH 1.96(1H,m,H-17),δH 1.05(3H,s,H-18),δH 1.32(3H,s,H-19),δH 1.47(3H,s,H-21),δH 2.62(1H,m,H-22a),δH 2.46(1H,m,H-22b),δH 6.00(1H,m,H-23),δH 5.67(1H,dt,H-24),δH 1.31(3H,s,H-26),δH 1.31(3H,s,H-27),δH 0.90(3H,s,H-28),δH 1.26(3H,s,H-29),δH 0.78(3H,s,H-30),δH 3.21(3H,s,-OCH3),δH 1.97(3H,s,CH3COO-),δH 5.48(1H,br s,H-1′),δH 4.84(1H,m,H-2′),δH 4.81(1H,m,H-3′),δH 4.72(1H,td,H-4′,J=3.4),δH 4.34(1H,dd,H-5a′),δH 4.27(1H,m,H-5b′),δH 4.83(1H,d,H-1″),δH 4.36(1H,d,H-2″),δH 4.06(1H,m,H-3″,J=9.2),δH 4.21(1H,dd,H-4″),δH 4.30(1H,t,H-5a″),δH 3.64(1H,d,H-5b″);13C NMR(150MHz,pyridine-d5)δC 36.0(C-1),δC 21.6(C-2),δC 79.6(C-3),δC 38.3(C-4),δC 51.3(C-5),δC 18.6(C-6),δC 36.7(C-7),δC 50.9(C-8),δC 54.3(C-9),δC 40.3(C-10),δC 77.0(C-11),δC 34.9(C-12),δC 41.8(C-13),δC 41.0(C-14),δC 31.6(C-15),δC 25.9(C-16),δC50.8(C-17),δC 17.5(C-18),δC 17.2(C-19),δC 74.5(C-20),δC 27.8(C-21),δC 44.7(C-22),δC 127.4(C-23),δC 138.6(C-24),δC 75.3(C-25),δC 26.3(C-26),δC 26.9(C-27),δC23.3(C-28),δC 30.3(C-29),δC 17.1(C-30),δC 106.7(C-1′),δC 84.3(C-2′),δC 79.8(C-3′),δC 86.1(C-4′),δC 63.3(C-5′),δC 102.8(C-1″),δC 73.0(C-2″),δC 75.1(C-3″),δC70.1(C-4″),δC 67.9(C-5″),δC 50.5(-OCH3),δC 171.1(CH3COO-),δC 21.0(CH3COO-)。
化合物8:青钱柳叶皂苷Z11(cyclocarioside Z11)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+775.4608(calculated for C41H68O12Na,found:775.4613);1H NMR(600MHz,pyridine-d5)δH 3.04(1H,m,H-1a),δH 1.84(1H,m,H-1b),δH 1.75(1H,m,H-2a),δH 1.66(1H,m,H-2b),δH 3.56(1H,m,H-3),δH 1.55(1H,m,H-5),δH 1.54(1H,m,H-6a),δH 1.45(1H,m,H-6b),δH 1.52(1H,m,H-7a),δH 1.16(1H,m,H-7b),δH 1.90(1H,m,H-9),δH 4.51(1H,m,H-11),δH 2.99(1H,m,H-12a),δH 1.68(1H,m,H-12b),δH 2.12(1H,m,H-13),δH 1.50(1H,m,H-15a),δH 1.03(1H,m,H-15b),δH 1.88(1H,m,H-16a),δH 1.80(1H,m,H-16b),δH 1.96(1H,m,H-17),δH 1.00(3H,s,H-18),δH 1.33(3H,s,H-19),δH 1.42(3H,s,H-21),δH 2.65(1H,m,H-22a),δH 2.50(1H,m,H-22b),δH 6.11(1H,m,H-23),δH 6.41(1H,dt,H-24),δH 5.05(1H,s,H-26a),δH 4.94(1H,s,H-26b),δH 1.83(3H,s,H-27),δH 0.88(3H,s,H-28),δH 1.25(3H,s,H-29),δH 0.76(3H,s,H-30),δH 5.52(1H,br s,H-1′),δH 4.86(1H,m,H-2′),δH 4.82(1H,m,H-3′),δH 4.73(1H,td,H-4′,J=3.4),δH 4.38(1H,dd,H-5a′),δH 4.27(1H,m,H-5b′),δH 5.06(1H,d,H-1″),δH 3.98(1H,d,H-2″),δH 4.20(1H,m,H-3″),δH 3.87(1H,dd,H-4″),δH 4.12(1H,t,H-5″),δH 4.52(1H,m,H-6a″),δH 4.33(1H,m,H-6b″);13C NMR(150MHz,pyridine-d5)δC 35.9(C-1),δC 21.5(C-2),δC 79.5(C-3),δC 38.2(C-4),δC 51.2(C-5),δC18.6(C-6),δC 36.5(C-7),δC 50.8(C-8),δC 54.2(C-9),δC 40.2(C-10),δC 77.1(C-11),δC35.0(C-12),δC 41.6(C-13),δC 41.0(C-14),δC 31.5(C-15),δC 25.9(C-16),δC 50.8(C-17),δC 17.3(C-18),δC 17.0(C-19),δC 74.7(C-20),δC 27.6(C-21),δC 45.1(C-22),δC128.6(C-23),δC 135.6(C-24),δC 142.9(C-25),δC 115.1(C-26),δC 19.1(C-27),δC 23.2(C-28),δC 30.2(C-29),δC 16.9(C-30),δC 106.6(C-1′),δC 84.4(C-2′),δC 79.7(C-3′),δC 85.8(C-4′),δC 63.2(C-5′),δC 102.2(C-1″),δC 75.6(C-2″),δC 78.7(C-3″),δC 78.0(C-4″),δC 72.6(C-5″),δC 63.8(C-6″)。
化合物9:青钱柳叶皂苷Z18(cyclocarioside Z18)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+793.4717(calculated for C41H70O13Na,found:793.4707);1H NMR(600MHz,pyridine-d5)δH 3.06(1H,m,H-1a),δH 1.85(1H,m,H-1b),δH 1.74(1H,m,H-2a),δH 1.67(1H,m,H-2b),δH 3.58(1H,br s,H-3),δH 1.56(1H,m,H-5),δH 1.55(1H,m,H-6a),δH 1.44(1H,m,H-6b),δH 1.52(1H,m,H-7a),δH 1.15(1H,m,H-7b),δH 1.89(1H,m,H-9),δH 4.48(1H,m,H-11),δH 2.97(1H,m,H-12a),δH 1.57(1H,m,H-12b),δH 1.81(1H,m,H-13),δH 1.39(1H,m,H-15a),δH 0.99(1H,m,H-15b),δH 1.77(1H,m,H-16a),δH 1.45(1H,m,H-16b),δH1.90(1H,m,H-17),δH 1.02(3H,s,H-18),δH 1.36(3H,s,H-19),δH 1.18(3H,s,H-21),δH1.75(1H,m,H-22a),δH 1.56(1H,m,H-22b),δH 2.04(1H,m,H-23a),δH 1.95(1H,m,H-23b),δH 3.96(1H,d,H-24),δH 1.47(3H,s,H-26),δH 1.41(3H,s,H-27),δH 0.89(3H,s,H-28),δH1.27(3H,s,H-29),δH 0.72(3H,s,H-30),δH 5.53(1H,br s,H-1′),δH 4.87(1H,m,H-2′),δH4.83(1H,m,H-3′),δH 4.74(1H,td,H-4′),δH 4.37(1H,dd,H-5a′),δH 4.28(1H,m,H-5b′),δH 5.16(1H,d,H-1″,J=7.7),δH 4.00(1H,d,H-2″,J=8.3),δH 4.29(1H,m,H-3″),δH 4.03(1H,dd,H-4″,J=8.1),δH 4.17(1H,t,H-5″,J=9.0),δH 4.54(1H,d,H-6a″,J=11.1),δH4.39(1H,m,H-6b″);13C NMR(150MHz,pyridine-d5)δC 36.1(C-1),δC 21.6(C-2),δC 79.6(C-3),δC 38.3(C-4),δC 51.3(C-5),δC 18.6(C-6),δC 36.6(C-7),δC 50.4(C-8),δC 54.4(C-9),δC 40.3(C-10),δC 77.3(C-11),δC 34.5(C-12),δC 41.8(C-13),δC 41.4(C-14),δC31.9(C-15),δC 27.1(C-16),δC 49.6(C-17),δC 17.3(C-18),δC 17.2(C-19),δC 86.8(C-20),δC 24.9(C-21),δC 34.8(C-22),δC 26.7(C-23),δC 84.6(C-24),δC 71.5(C-25),δC26.5(C-26),δC 28.0(C-27),δC 23.2(C-28),δC 30.3(C-29),δC 17.1(C-30),δC 106.7(C-1′),δC 84.4(C-2′),δC 79.7(C-3′),δC 85.9(C-4′),δC 63.3(C-5′),δC 102.1(C-1″),δC75.7(C-2″),δC 79.0(C-3″),δC 78.1(C-4″),δC 72.8(C-5″),δC 63.8(C-6″)。
化合物10:青钱柳叶皂苷Z19(cyclocarioside Z19)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+,835.4820(calculated for C43H72O14Na,found:835.4818);1H NMR(600MHz,pyridine-d5)δH 3.06(1H,m,H-1a),δH 1.83(1H,m,H-1b),δH 1.74(1H,m,H-2a),δH 1.64(1H,m,H-2b),δH 3.54(1H,br s,H-3),δH 1.55(1H,m,H-5),δH 1.53(1H,m,H-6a),δH 1.40(1H,m,H-6b),δH 1.51(1H,m,H-7a),δH 1.17(1H,m,H-7b),δH 1.88(1H,m,H-9),δH 4.48(1H,m,H-11),δH 2.97(1H,m,H-12a),δH 1.59(1H,m,H-12b),δH 1.81(1H,m,H-13),δH 1.39(1H,m,H-15a),δH 1.00(1H,m,H-15b),δH 1.79(1H,m,H-16a),δH 1.43(1H,m,H-16b),δH1.90(1H,m,H-17),δH 1.02(3H,s,H-18),δH 1.35(3H,s,H-19),δH 1.19(3H,s,H-21),δH1.77(1H,m,H-22a),δH 1.55(1H,m,H-22b),δH 2.03(1H,m,H-23a),δH 1.95(1H,m,H-23b),δH 3.96(1H,d,H-24),δH 1.48(3H,s,H-26),δH 1.42(3H,s,H-27),δH 0.90(3H,s,H-28),δH1.27(3H,s,H-29),δH 0.73(3H,s,H-30),δH 1.97(3H,s,CH3COO-),δH 5.50(1H,br s,H-1′),δH 4.87(1H,m,H-2′),δH 4.63(1H,m,H-3′),δH 4.74(1H,td,H-4′),δH 4.81(1H,dd,H-5a′),δH 4.61(1H,m,H-5b′),δH 5.16(1H,d,H-1″,J=7.7),δH 3.99(1H,d,H-2″,J=8.3),δH 4.30(1H,m,H-3″),δH 4.03(1H,dd,H-4″,J=8.1),δH 4.17(1H,t,H-5″,J=9.0),δH4.54(1H,d,H-6a″,J=11.1),δH 4.36(1H,m,H-6b″);13C NMR(150MHz,pyridine-d5)δC 36.0(C-1),δC 21.7(C-2),δC 80.0(C-3),δC 38.2(C-4),δC 51.2(C-5),δC 18.6(C-6),δC 36.6(C-7),δC 50.4(C-8),δC 54.4(C-9),δC 40.3(C-10),δC 77.3(C-11),δC 34.5(C-12),δC41.4(C-13),δC 50.4(C-14),δC 31.9(C-15),δC 28.0(C-16),δC 49.6(C-17),δC 17.1(C-18),δC 17.1(C-19),δC 86.8(C-20),δC 24.9(C-21),δC 34.8(C-22),δC 26.7(C-23),δC84.6(C-24),δC 71.5(C-25),δC 26.5(C-26),δC 28.0(C-27),δC 23.2(C-28),δC 30.2(C-29),δC 17.3(C-30),δC 106.9(C-1′),δC 84.5(C-2′),δC 80.0(C-3′),δC 81.8(C-4′),δC65.4(C-5′),δC 102.1(C-1″),δC 75.7(C-2″),δC 79.0(C-3″),δC 78.1(C-4″),δC 72.8(C-5″),δC 63.8(C-6″),δC 171.1(CH3COO-),δC 21.0(CH3COO-)。
化合物11:青钱柳叶皂苷Z12(cyclocarioside Z12)
白色粉末,易溶于甲醇,吡啶.HRESIMS m/z[M+Na]+677.3877(calculated for C35H58O11Na,found:677.3880);1H NMR(600MHz,pyridine-d5)δH 3.01(1H,m,H-1a),δH 1.83(1H,m,H-1b),δH 1.81(1H,m,H-2a),δH 1.69(1H,m,H-2b),δH 3.64(1H,t,H-3),δH 1.55(1H,m,H-5),δH 1.47(1H,m,H-6a),δH 1.41(1H,m,H-6b),δH 1.52(1H,m,H-7a),δH 1.10(1H,m,H-7b),δH 1.85(1H,m,H-9),δH 4.46(1H,dt,H-11),δH 2.58(1H,m,H-12a),δH 1.55(1H,m,H-12b),δH 2.21(1H,m,H-13),δH 1.48(1H,m,H-15a),δH 1.05(1H,m,H-15b),δH 1.90(1H,m,H-16a),δH 1.70(1H,m,H-16b),δH 2.55(1H,m,H-17),δH 1.02(3H,s,H-18),δH 1.34(3H,s,H-19),δH 2.07(3H,s,H-21),δH 0.95(3H,s,H-28),δH 1.29(3H,s,H-29),δH 0.70(3H,s,H-30),δH 5.56(1H,br s,H-1′),δH 4.87(1H,m,H-2′),δH 4.84(1H,m,H-3′,J=7.9),δH 4.75(1H,m,H-4′),δH 4.39(1H,dd,H-5a′,J=12.0),δH 4.28(1H,dd,H-5b′,J=11.7,4.4),δH 4.87(1H,dd,H-1″,J=15.9),δH 3.94(1H,t,H-2″,J=8.4),δH 4.11(1H,t,H-3″,J=8.8),δH 3.69(1H,t,H-4″,J=8.8),δH 3.63(1H,m,H-5″),δH 1.62(1H,t,H-6″,J=5.9);13C NMR(150MHz,pyridine-d5)δC 36.1(C-1),δC21.8(C-2),δC 79.7(C-3),δC 38.4(C-4),δC 51.4(C-5),δC 18.7(C-6),δC 36.9(C-7),δC50.5(C-8),δC 54.2(C-9),δC 40.5(C-10),δC 76.6(C-11),δC 33.1(C-12),δC 43.3(C-13),δC 41.9(C-14),δC 31.8(C-15),δC 27.1(C-16),δC 54.3(C-17),δC 17.5(C-18),δC 17.0(C-19),δC 211.3(C-20),δC 30.5(C-21),δC 23.4(C-28),δC 30.4(C-29),δC 16.4(C-30),δC 106.9(C-1′),δC 84.6(C-2′),δC 79.7(C-3′),δC 86.1(C-4′),δC 63.4(C-5′),δC 102.0(C-1″),δC 76.0(C-2″),δC 78.8(C-3″),δC 77.3(C-4″),δC 73.1(C-5″),δC 19.1(C-6″)。
实施例3
达玛烷型三萜皂苷化合物1-11的生物活性测定
3.1化合物1-11抑制α糖苷酶活性以及化合物1和2对酶活性与反应时间的测定
3.1.1α-葡萄糖苷酶活性抑制率测定
测试中以阿卡波糖为阳性对照药,所有待测化合物均用磷酸盐缓冲液(pH=6.9)稀释成不同浓度(0.001、0.01、0.05、0.1、0.2、0.5mg·mL-1)的样品溶液。在96孔板中加入50μL的各浓度化合物溶液,50μL的磷酸缓冲液,再加入100μL0.2U·mL-1的α-葡萄糖苷酶溶液,恒温37度孵育10min,然后加入50μL2mmol·L-1的对硝基苯基-β-D-吡喃半乳糖苷(PNPG),继续在37℃条件下孵育5min,最后在405nm波长处测定吸光度(A)值。抑制率(%)=[A1-(A2-A3)]/A1*100%,其中A1:用缓冲液代替样品;A2:待测样品;A3:用缓冲液代替PNPG。表1为各待测化合物1-11的酶活性抑制率IC50值。
3.1.2化合物1和2对酶活性与反应时间的测定
测定了化合物1和2(0.5mg·mL-1)在1、5、10、15min内酶速反应的影响,50μL样品(用0.1mM PH6.8的PBS溶解)+50μL PBS(0.1mM,PH6.8)+100μLα-糖苷酶(0.2U/mL用0.1MPH6.8的PBS稀释)+50μL 2mM PNPG(用0.1M PH6.8的PBS稀释),测定酶活性抑制率-反应时间的关系。
3.2化合物1-11对NO释放,以及活性化合物2抑制炎症因子内源性mRNA和蛋白表达的影响测定
3.2.1细胞毒性实验:
细胞抗炎实验分组:将实验分为:①空白组:RAW264.7细胞不加入任何药物;②LPS组:细胞+5ng/mL的LPS溶液;③加药组:细胞+5ng/mL的LPS溶液+不同浓度阳性对照或化合物;
MTT实验方法:①细胞培养:将RAW264.7细胞进行消化,进行细胞计数,将细胞浓度调整至1×10 5个/mL;②种板:按照180μL/孔的细胞悬液接种于96孔板中,在37℃孵育24小时;③加LPS:换新鲜培养基180μL,在每孔加入10μL的浓度为5ng/mL的LPS溶液,在37℃孵育2个小时;④加药:把不同浓度的阳性对照和不同浓度的化合物,各10μL加入孔板,每个样设定三个复孔,于37℃培养24个小时;⑤加MTT:每孔加MTT溶液,37℃培养4个小时;⑥加DMSO:弃掉上清液,每孔加入100μL DMSO,震荡15min,完全溶解甲臜;⑦测OD值:将96孔板置于酶标仪中,选择波长为490nm,测定OD;⑧计算:计算细胞存活率;
3.2.2达玛烷型三萜皂苷化合物抑制NO活性
Griess法测LPS诱导RAW264.7巨噬细胞NO的含量,ELISA法测TNF-α、PGE2和IL-6的含量:①RAW264.7细胞的培养与步骤3.2.1相同,96孔板换成24孔板,细胞加入体积和加药量体积比原来扩大4倍即可;②加药:对加药组按照要求进行加药,一一标识;③取样:收集上清液于离心管中,离心、进行下一步试剂盒操作;④NO的测试步骤按试剂盒说明书进行,最后根据抑制率和浓度的关系计算IC50值:
NO抑制率(%)=[(ALPS组-A药物组)/(ALPS组-A空白组)]×100%。
3.2.3采用qRT-PCR技术探讨化合物2对iNOS﹑NF-κB﹑COX-2﹑IL-6﹑IL-1β﹑TNF-α的内源性mRNA水平的释放的影响
3.2.3.1RNA提取
采用上述细胞培养的方法进行细胞培养,取对数生长期细胞用于后期实验,将培养好的RAW264.7细胞处理好之后接种到大皿中,加入10mL的培养基培养12h后观察细胞状态,细胞分化较小,密度达到60%左右进行换液加药,1h后加入LPS,作用12h后,运用RNA提取试剂盒进行总RNA的提取。紫外分光光度计分别测定A260及A280下OD值,要求A260/A280比值介于1.8~2.1,根据A260计算总RNA含量,-80℃保存备用。
3.2.3.2逆转录反应
按试剂盒说明。50ng-3μg总RNA可建立20μL反应体系。将模板RNA在冰上解冻;5×goNA Buffer,FQ-RT Prime Mix,10×King RT Buffer,RNase-Free ddH2O,Fastking RTEnzyme Mix室温解冻,解冻完全后立即至于冰上,使用前漩涡震荡均匀,离心备用。按表格1中的方法配置gDNA去除体系,配置完成后混匀离心,在42℃孵育3min后迅速至于冰上,按照表1与2配制每孔10μL的反转录反应体系。
表1中配置gDNA去除体系的方法
表2反转录反应体系混合液的配制方法
将配制好的反转录反应液加入gDNA去除步骤的反应液中,充分混匀。漩涡震荡之后离心数秒。在仪器上孵育(42℃孵育15min;95℃孵育3min)之后得到cDNA,放于冰上用于PCR或转移到-20℃保存。
3.2.3.3荧光定量PCR
将cDNA加入80μL无酶水稀释,按照扩增试剂盒步骤建立20μL体系,所用引物按照1:100稀释。用7500Software v2.0.4软件进行后续实验。qRT-PCR反应条件分别为:设置程序(50℃20s;95℃2min;95℃10s;60℃34s;72℃30s;95℃1min;55℃1min;98℃14min 33s)。
3.2.3.4不同基因PCR引物序列
不同基因PCR引物序列见表3。
表3各引物序列
3.2.4Western-blot法测定化合物2对细胞中iNOS、COX-2和NF-κB/p65蛋白的表达
3.2.4.1蛋白样品制备和蛋白定量:①细胞培养与步骤3.2.1相同;②提取细胞蛋白收集细胞,加细胞裂解液,离心,收集细胞蛋白;③BCA(喹啉酸)法蛋白进行定量,上样蛋白量的确定;
3.2.4.2蛋白质变性:加上样缓冲液,煮沸,置到冰上冷却;备用(3)SDS-PAGE电泳:①制分离胶:根据所有蛋白的分子量来确定相应分离胶的配比,制备分离胶;②加浓缩胶:分离胶凝固后,灌5%浓缩胶至分离胶顶端;然插入梳子;③取胶至电泳槽:浓缩胶凝固,取出梳子,将胶板从固定钳中取下,冲水,置于电泳槽,玻璃板的高端向外;④上样:按从左到右的顺序加Marker和样品蛋白;⑤电泳:初设电压80V,带样品跑至分离胶部分,电压调为100V,至各组蛋白置合适位置,结束电泳;
3.2.4.3转膜:在电转移仪夹子二面依次铺好海绵垫和三层滤纸,将胶转移到滤纸上,将合适大小的硝酸纤维素膜盖于胶上,盖3张滤纸,除气泡,合起夹子,装好电转移仪(注意电极对应),根据不同蛋白需要选定所需的电流和时间;
3.2.4.4免疫反应:①封闭:取出PVDF膜,加入在装有10mL封闭液的玻璃皿中,在摇床上缓慢摇动2h或者4℃过夜;②孵育一抗:用TBST洗过的洗膜,膜蛋白面朝下,放于抗体液面上;室温下孵育1-2h后,用TBST在室温下摇床上洗三次,每次10min;③孵育二抗:二抗稀释液并与膜接触,孵育1-2h后,TBST与摇床洗三次,每次10min,准备进行下一步;
3.2.4.5化学发光显影:凝胶图像分析:加入显影液用,将PVDF进行拍照处理;
3.3数据处理:用凝胶图像处理系统分析目标蛋白的净光密度值,所有数值是三次测定的平均值±SE。**p<0.01与LPS处理的细胞相比。
3.4实验结果
3.4.1化合物1-11抑制α糖苷酶的活性以及化合物1和2的动力学研究
3.4.1.1化合物1-11抑制α糖苷酶的活性
化合物1-11抑制α糖苷酶的活性其结果见表4。从表4可知,除了化合物6、9和10外,其他化合物对α糖苷酶有很好的抑制活性,它们的IC50在257.74μM至578.77μM之间,其中化合物1、2、3和8的抑制α糖苷酶活性优于阳性对照阿卡波糖的活性。
表4化合物1-11对α-葡萄糖苷酶活性的影响a
aAll values are means of three independent experiments。
bAcarbose,a hypoglycemic drug used as positive control。
3.4.1.2化合物1和2对酶活性与反应时间的测定
化合物1和2对抑制酶活性与反应时间的影响见图1。从图1可知,化合物1和2抑制α糖苷酶的活性随着时间延长而逐渐减弱。
3.4.2化合物1-11对NO释放,以及活性化合物2抑制炎症因子内源性mRNA和蛋白表达的影响
3.4.2.1化合物1-11对RAW 264.7细胞释放NO的抑制作用
化合物1-11对RAW 264.7细胞释放NO的抑制作用见表5。从表5可知,化合物1和2显示显著地抑制RAW264.7细胞NO的释放,它们的IC50分别是9.10μM至9.02μM,抑制活性与阳性对照地塞米松(Dexamethasone,IC50是9.17μM)的相当,化合物3-7和9-10也显示抑制RAW264.7细胞释放NO的活性,表明青钱柳中含有抗炎活性良好的活性达玛烷型皂苷类化合物。
表5化合物对RAW 264.7细胞释放NO的抑制作用a
aAll values are means of three independent experiments。
bDexamethasone,an anti-inflammatory agent used as positive control。
3.4.2.2化合物2抑制炎症因子内源性mRNA表达的影响
化合物2抑制炎症因子iNOS(A)﹑NF-κB(B)﹑COX-2(C)﹑IL-6(D)﹑IL-1β(E)﹑TNF-α(F)内源性mRNA表达的结果见图2。从图2可知,LPS刺激提高了iNOS(A)﹑NF-κB(B)﹑COX-2(C)﹑IL-6(D)﹑IL-1β(E)﹑TNF-α(F)的内源性mRNA水平,而化合物2能够抑制iNOS(A)﹑NF-κB(B)﹑COX-2(C)﹑IL-6(D)﹑IL-1β(E)﹑TNF-α(F)的内源性mRNA的水平,并且存在浓度梯度抑制效果。
3.4.2.3化合物2对iNOS、COX-2和NF-κB/p65蛋白表达的影响
化合物2抑制iNOS、COX-2和NF-κB/p65蛋白表达的结果见图3。从图3可知,化合物2能够抑制iNOS、COX-2和NF-κB/p65蛋白表达,并且存在浓度梯度抑制效果。
最后应说明的是:以上所述仅为本发明的优选实施例而已,并不用于限制本发明,尽管参照前述实施例对本发明进行了详细的说明,对于本领域的技术人员来说,其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (4)
2.权利要求1所述的达玛烷型三萜皂苷类化合物的制备方法,其特征在于:包括如下步骤:
S1:取10kg干燥的青钱柳叶,加入75%乙醇水溶液,依次加热回流提取3次,时间为3小时、2小时、2小时,合并滤液,减压回收乙醇,得浸膏2.10kg;
S2:取浸膏1.5kg悬浮于20L水中,经D101大孔吸附树脂色谱柱吸附,用水清洗,然后用30%、95%乙醇洗脱,分别得到30%、95%乙醇洗脱物250g、625.0g,该洗脱物作为富含达玛烷型三萜皂苷的青钱柳叶提取物;
S3:将步骤S2制备的95%乙醇洗脱物150.0g,经硅胶柱层析,以二氯甲烷-甲醇100:0、60:1、20:1、10:1、8:1、4:1、2:1、0:100为洗脱剂进行梯度洗脱,得到Fr.A 22g、Fr.B 16g、Fr.C 23g、Fr.D 15g、Fr.E 27g、Fr.F 19g、Fr.G 13g和Fr.H 6g;
将组分Fr.F19g经过反相C18硅胶柱层析,以水-甲醇100:0-0:100为洗脱剂进行梯度洗脱,得到6个组分为0.5g Fr.F.1、3.5g Fr.F.2、4.2g Fr.F.3、2.5g Fr.F.4、1.5g Fr.F.5和1.1g Fr.F.6;
将组分4.2g Fr.F.3经过反相C18硅胶柱层析MeOH-H2O,60:40→100:0,得到300mgFr.F.3.1、1315mg Fr.F.3.2、345mg Fr.F.3.3、870mg Fr.F.3.4、460mg Fr.F.3.5和234mgFr.F.3.6;
1315mg Fr.F.3.2经过反相C18硅胶柱层析制备色谱、采用50%乙腈半制备液相色谱,得到10.7mg化合物2、6.2mg化合物11和7.1mg化合物9;
将组分345mg Fr.F.3.3经过葡聚糖凝胶Sephadex LH-20、反相C18硅胶柱层析及50%乙腈半制备液相纯化,得到6.2mg化合物3、5.0mg化合物4、4.7mg化合物5和7.5mg化合物10;
将组分870mg Fr.F.3.4经过制备、78%甲醇半制备反相C18硅胶柱层析,得到4.1mg化合物6和6.6mg化合物7;
将组分Fr.F.3.5经过反相C18硅胶柱层析,葡聚糖凝胶Sephadex LH-20/50%乙腈半制备反相C18硅胶柱层析,得到14.3mg化合物1和7.4mg化合物8。
3.权利要求1所述的达玛烷型三萜皂苷类化合物在制备降糖和抗炎药物中的应用,其特征在于:所述的达玛烷型三萜皂苷类化合物为1-5和7化合物的任意一种或几种。
4.权利要求1所述的达玛烷型三萜皂苷类化合物在制备降糖和抗炎药物中的应用,其特征在于:所述的达玛烷型三萜皂苷类化合物为1-5和7化合物的一种或几种与药学可接受的赋形剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010571725.1A CN111574579B (zh) | 2020-06-22 | 2020-06-22 | 达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010571725.1A CN111574579B (zh) | 2020-06-22 | 2020-06-22 | 达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111574579A CN111574579A (zh) | 2020-08-25 |
CN111574579B true CN111574579B (zh) | 2022-12-13 |
Family
ID=72120232
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010571725.1A Active CN111574579B (zh) | 2020-06-22 | 2020-06-22 | 达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111574579B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115724900B (zh) * | 2022-12-14 | 2024-06-07 | 广西师范大学 | 达玛烷型三萜皂苷类化合物及其制备方法和在制备降血糖药物中的应用 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060025393A1 (en) * | 1999-04-30 | 2006-02-02 | Shutsung Liao | Steroid derivatives |
CN101899083B (zh) * | 2010-07-28 | 2012-11-21 | 南京林业大学 | 青钱柳酸a的制备方法 |
CN107778340A (zh) * | 2017-10-18 | 2018-03-09 | 中国科学院昆明植物研究所 | (20S,24R)‑20,24‑环氧达玛烷‑3β,12β,25‑三醇及其应用 |
CN109364119B (zh) * | 2018-12-26 | 2021-10-01 | 浙江大学 | 从青钱柳叶中制备具有降血糖作用的总三萜的方法及应用 |
CN110201025B (zh) * | 2019-05-31 | 2021-06-18 | 温州医科大学 | 青钱柳提取物在制备治疗或防治糖尿病心肌病药物中的应用 |
CN110746474B (zh) * | 2019-11-14 | 2022-10-04 | 广西师范大学 | 达玛烷型三萜皂苷类化合物及其制备方法和在制备抗炎药物中的应用 |
CN110922444B (zh) * | 2019-12-06 | 2022-04-15 | 天津中医药大学 | 具有抗炎活性的人参二醇型三萜皂苷 |
-
2020
- 2020-06-22 CN CN202010571725.1A patent/CN111574579B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN111574579A (zh) | 2020-08-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
De Tommasi et al. | Characterization of three new triterpenoid saponins from Ardisia japonica | |
CN101279964B (zh) | 愈创木烷型倍半萜、其制备方法及其医药用途 | |
GB2360519A (en) | Steroidal glycosides | |
CA1148936A (en) | Triterpenic saponin having pharmacological potency | |
Li et al. | α-Glucosidase inhibitory and anti-inflammatory activities of dammarane triterpenoids from the leaves of Cyclocarya paliurus | |
Warashina et al. | Steroidal glycosides from the aerial part of Asclepias incarnata | |
Ma et al. | New pregnane glycosides from the roots of Cynanchum otophyllum | |
Alkefai et al. | New olean-15-ene type gymnemic acids from Gymnema sylvestre (Retz.) R. Br. and their antihyperglycemic activity through α-glucosidase inhibition | |
CN111574579B (zh) | 达玛烷型皂苷制备方法及其在制备降糖和抗炎药物、保健品中的应用 | |
CN106220701A (zh) | 三萜化合物及其制备方法与应用 | |
Chen et al. | Triterpenoid Saponins from Gypsophila altissima L. | |
Si-Yuan et al. | New triterpenoid saponins from the leaves of Ilex chinensis and their hepatoprotective activity | |
CN110922444B (zh) | 具有抗炎活性的人参二醇型三萜皂苷 | |
CN111574573A (zh) | 十五种苯乙醇苷类化合物及其分离纯化方法与应用 | |
Contreras et al. | Hypoglycemic activity of a new carbohydrate isolated from the roots of Psacalium peltatum | |
CN101724008A (zh) | 通光藤c21甾体苷转化产物及其制备方法和用途 | |
CN106083876A (zh) | 盐酸阿糖胞苷的药物组合物及其在生物医药中的应用 | |
CN105837595A (zh) | 阿替洛尔的药物组合物及其在生物医药中的应用 | |
CN113321696B (zh) | 一种强心苷的制备方法及其在制备抗肿瘤药物中的应用 | |
CN113004299B (zh) | 山竹皮中具有降低餐后血糖的呫吨酮类化合物及其提取方法和应用 | |
Hao et al. | Six new steroidal glycosides from roots of Cynanchum bungei | |
Li et al. | A new triterpenoid saponin from the leaves and stems of Panax quinquefolium L. | |
CN113801130A (zh) | 地胆草中吉玛烷型倍半萜内酯类化合物及其制备方法和应用 | |
WO2013097661A1 (zh) | 呋甾烷型皂苷衍生物及其用途 | |
Yin et al. | Saikosaponins from Bupleurum chinense and inhibition of HBV DNA replication activity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |