Discovery Of Quinone Reductase Inducers From Triperygium Wilfordii

Tripterygium wilfordii Hook.f. is one of the most important crude drugs in traditional Chinese medicine and have been used for the treatment of rheumatoid arthritis and other autoimmune diseases.PhaseⅡenzymes play important roles in the metabolism of chemical carcinogens and other harmful oxidants, and quinone reductase is one of them. The increase of phaseⅡenzymes levels are considered as the major mechanism of prevention of cancer. The chemical compounds which can induce the quinone reductase are regarded having the chemopreventive effects in the initiation of many tumors.In this paper, traditional separation with activity tracking combined with LC-MS are used for the analysis of T. wilfordii. The main innovation and academic contributions of this thesis are presented as follows:1. Column chromatography was used to separate constituents from the ethyl acetate partition in 95% ethanol extract of T. wilfordii and the structures of twenty one compounds were elucidated by IR, UV, MS, NMR and physicochemical properties. Seven new compounds were identified as triptobenzene Y (1), wilforsinines C-H (2-7), and fourteen known compounds were identified as triptobenzene H (8), triptinin B (9), ejap-3 (10), celastrine A (11), 1α,2α,6β,8α,15-pentacetoxy-9a-benzoyloxy-β-agarofu ran (12), ejap-4 (13), 1α,6β,8α,13-tetraacetoxy-9α-benzoyloxy-2α-hydroxy-β-dih ydroagarofuran (14), triptobenzene A (15), blumenol C (16), celangulatin F (17), wilforsinine B (18),2β,6α,12-triacetoxy-1β,9β-bis (benzoyloxy)-8β-(β-nicotinoyloxy)-β-dihydroagarofuran (19),2β,5α,7β-triacetoxy-11-isobutyryloxy-8a-β-furancarbo nyloxy)-4α-hydroxy-1β-nicotinoyloxy-dihydroagarofuran (20) and wilfosinine A (21). 2. The LC-MS method was employed to study the chemical components which were able to induce QR in ethyl acetate partition of 95% ethanol extract of T. wilfordii based on components change after reacting with GSH and two compounds which had QR induction effects were identified.3. Hepa 1c1c7 murine hepatoma cells were employed to assay the QR activities of the partitions and components from the 95% ethanol extract of T. wilfordii.