Investigation Of Bioactive Constituents Of Tacca Chantrieri And Rheum Tataricum

This thesis includes three parts:Part one:Literature reviewA review about research progress on the chemical constituents and biological activity of Tacca chantrieri and Rheum were presented.Part two:Experimentation1Bioassay-guided chemical investigation of Tacca chantrieriBioassay-guided chemical investigation of the roots and rhizomes of Tacca chantrieri. Ten taccalonolides were isolated by using flash chromatography, semi-pre HPLC. Their structures were determined by extensive spectroscopic analysis, including2D-NMR data. One is a new compound, taccalonolide AT, nine are confirmed as known taccalonolides, they are taccalonolide A, B, E, N, R, T, AO, AP, AL. In addition, taccalonolide AP, AL are isolated from Tacca chantrieri for the first time.2Cytotoxicity constituents investigation of Rheum tataricum2.1Phytochemistry investigation of Rheum tataricumSilica gel, Sephadex LH-20column chromatography and High Performance Liquid Chromatography were used to do isolation. The structures of isolates were confirmed by spectral (LC/MS,1H-NMR,13C-NMR,2D-NMR) and thin-layer chromatography analysis, and by comparison with the literature reports.11compounds were isolated, they are chrysophanol (1), emodin (2), physcion (3), aloe-emodin (4), rheosmin (5),1,3,8-trihydroxyanthraquinone (6), sitosterol (7), daucosterol(8), emodin-8-O-β-(6’-O-acety)glucopyranoside(9), physcion-1-O-β-(6’-O-acety)glucopyranoside (10), chrysophanol-1-O-β-(6’-O-acety)glucopyranoside (11). Compound (4)-(11) were isolated from this species for the first time.2.2Cytotoxicity screeningCompound4,5,6,9,10,11were evaluated the cytotoxic activity, as a result, compound4,6,9,10,11have cytotoxic activity against HeLa cells. 2.3Cytotoxicity mechanism of aloe-emodin and1,3,8-trihydroxyanthraquinoneTo investigate the cytotoxicity mechanism of aloe-emodin and1,3,8-trihydroxy--anthraquinone, cell cycle analysis, indirect immunofluorescence, intracellular signaling antibody array as well as immunoblotting were conducted. The results suggest that the both compounds induce cell death at least partially through apoptosis. In addition,1,3,8-trihydroxyanthraquinon activated the mTORCl signaling.Part three:Summary and discussionFrom the study conducted in this paper, a conclusion can be made that:first of all, the review of the research progress on the chemical constituents and pharmacological activities of Tacca chantrieri Andre showed that chemical constituents of Tacca chantrieri are complicated, including taccalonolides, saponins, diarylheptanoides and other glycosides; in addition, it has antibacterial, antihypertensive and antitumor activities. Bioassay guided isolation showed that taccalonolides have the microtubule stabilizer activity, ten taccalonolides were isolated, one is new taccalonolide; what’s more, more than one gram taccalonolide A and half gram taccalonolide E were obtained and they can be used as the material to do semi-synthesis for further investigation of the structure activity relationship of taccalonolides to find more potential microtubule stabilizer agents for clinical. Second, the major constituent of Rheum tataricum is anthraquinone and the glycosides, similar to other species in Rheum genus. Eleven compounds were isolated from Rheum tataricum, eight are anthraquinone and their glycoside, eight are isolated from this species for the first time; six compounds were evaluated the cytotoxic activity against HeLa cells, in addition, cytotoxicity mechanism of aloe-emodin and1,3,8-trihydroxyanthraquinone were investigated, as a result, these two compound induce cell death at least partially through apoptosis,1,3,8-trihydroxy anthraquinon activated the mTORC1signaling.