| The genus Cimicifuga(Ranunculaceae)comprises about 28 species distributed widely in the world.C.dahurica,C.foetida,and C.heracleifolia are officially li sted in the Chinese Pharmacopoeia.Rhizoma Cimicifugae have been widely used in various formulations of traditional Chinese medicine as an antipyretic,antitox ic,antitumor,analgesic and anti-inflammatory agents.In the current study,chemical constituents of the rhizome of C.foetida from Northeast China and their antitumor activities were firstly investigated.Two dime ric 3-prenylindole aromatic-alkyl cycloaddition derived quinone alkaloids,cimicifo etones A and B,were isolated and they exhibited promising anti-proliferative acti vity against HL-60 cells.Furthermore,another C.foetida from northeast China a nd one from North Korea were further studied by using acid-base extraction.Wit h modern chromatography and spectroscopic techniques,nineteen compounds wer e isolated and identified from these studies.Their structures were identified as:c imicifoetone A(1);cimicifoetone B(2);7,8-didehydrocimigenol(3);acerinol(4);24-epi-24-O-acetyl-7,8-didehydrohydroshengmanol(5);cimigenol-3-O-?-D-xylopyra noside(6);24-epi-7,8-didehydrocimigenol-3-O-?-D-xylopyranoside(7);24-epi-24-O-acetyl-7,8-didehydrohydroshengmanol-3-o-?-D-xylopyranoside(8);daucosterol(9);cimifugin(10);cimicifugamide(11);kellol(12);3-xylosyl-24-O-acetylhydroshen gmanol-15-glucoside(13);cimigenol(14);24-O-acetyl-25-anhydroshengmanol-3-?-D-xylopyranoside(15);25-acetylcimigenol-3-O-?-D-xyloside(16);25-anhydrocimi genol-3-O-?-xyloside(17);acetyl-shengmanol-3-O-?-xyloside(18);?-sitosterol(19).Among them,compounds 1 and 2 were two dimeric 3-prenylindole aromatic-alkyl cycloaddition derived quinone alkaloids,compound 11 was a phenolic amid e compound,compounds 10 and 12 were two chromones compounds,compounds 9 and 19 wee steroidal compounds,the other 12 compounds were cycloartane tr iterpenoids.Through the method of acid-base extraction,we did not found cimicifoetone A and cimicifoetone B in the second C.foetida material from northeast China and North Korea.The rest extract was then enriched by using D101 macroporous re sinand the 95%EtOH elution fraction was then separated through Sephadex LH-20 gel column and preparative TLC.Cimicifoetones A and B were then successf ully obtained.Cimicifoetones A and B exhibited promising anti-proliferative activity against t he HL-60?A549?NCI-H1975?Colo-205?A375?MKN7?GSU cell lines with I Cso in the range of 1.36-21.09?M.For HL-60 cells,cimicifoetone B showed th e most cytotoxic activity with IC50 among these results,which was further studie d for its action mechanism by flow cytometric and western blot analysis.The re sults showed that cimicifoetone B significantly increased the expression of active-caspase-3,-8,and-9.Furthermore,PARP cleavage was also evoked.The pro-apo ptotic protein,Bax,was up-regulated,and the antiapoptotic proteins,Bcl-2,Bcl-x L was down-regulated by cimicifoetone B.The cytosolic levels of cytochrome c were also increased in a concentration-dependent manner.The results revealed tha t cimicifoetone B induced cell apoptosis via the intrinsic and extrinsic pathways.In addition,hepatoprotective activities of cycloartane triterpenoids were evaluated on H2O2 induced cell damage model in HepG2 and these compounds did not s how hepatoprotective activity. |
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