中国药理学通报Issue(8)：1147-1151,1152,6.DOI:10.3969/j.issn.1001-1978.2015.08.024
头花蓼水提取物对CYP450酶诱导和抑制作用研究
Inhibitory and inductive effects of Polygonum capitatum water extract on CYP450
摘要
Abstract
Aim To evaluate the inhibitive and induc-tive effects of Polygonum capitatum water extract on main cytochrome P450 isoforms in human and liver mi-crosomes of mouse in vitro for predicting the herb-drug interactions in clinical application. Methods The in vitro inhibitory effect was evaluated by incubating Po-lygonum capitatum water extract with the probe sub-strates of main phase I metabolic enzymes in human liver microsomes, including CYP1A2, CYP2E1, CYP2C9,CYP2C19 and CYP3A4. Mice were adminis-tered with Polygonum capitatum water extract at dosage of 0 . 58 g · kg-1 and 1 . 16 g · kg-1 by gastric lavage for successive 7 days and 14 days, then the cocktail-LC-MS/MS method was applied to assess the inductive effect of main CYP450 isoforms in mouse liver micro-somes. Results The IC50 values of Polygonum capita-tum water extract on main CYP450 isoforms in human liver microsomes were from 849 . 6 mg · L-1 to 2 287 mg·L-1 . Compared with the blank control group, the activites of CYP2C9 and CYP3A4 in 1. 16 g·kg-1 7 d group were about 49 . 9 % and 21. 1 % higher ( P <0. 01, P < 0. 05 ) respectively, the activities of CYP2C9 and CYP3A4 in 0. 58 g·kg-1 7 d group were 27. 6 % and 15. 5 % higher ( P <0. 01 , P <0. 05 ) respectively, the activities of CYP2C9 and CYP3A4 in 1. 16 g·kg-1 14 d group were 67. 5 % and 32. 1 %higher (P<0. 01) respectively, while the activities of CYP1 A2 , CYP2 E1 and CYP2 C19 were not increased significantly in Polygonum capitatum treatment group. Conclusions Polygonum capitatum water extract do not show the inhibitory effect on main CYP450 in hu-man liver microsomes. There is induction on CYP2C9 and CYP3 A4 in mouse liver microsomes by Polygonum capitatum water extract.关键词
头花蓼水提取物/CYP450 酶/酶抑制/酶诱导/药物相互作用/肝微粒体Key words
Polygonum capitatum water extract/CYP450 enzyme/enzyme inhibition/enzyme induc-tion/herb-drug interaction/liver microsomes分类
医药卫生引用本文复制引用
陆苑,潘洁,谢玉敏,郑林,黄勇,王永林,李勇军..头花蓼水提取物对CYP450酶诱导和抑制作用研究[J].中国药理学通报,2015,(8):1147-1151,1152,6.基金项目
国家科技支撑计划课题(No 2013BAI11B01) （No 2013BAI11B01）
贵州省科技重大专项项目(黔科合重大专项字[2011]6019号) （黔科合重大专项字[2011]6019号）
贵州省中药现代化科技产业研究开发专项(黔科合 ZY 字[2013]3020号,黔科合中药字[2013]5062号) （黔科合 ZY 字[2013]3020号,黔科合中药字[2013]5062号）
贵州省中药现代化科技产业研究开发专项(黔科合重G字[2013]4001) （黔科合重G字[2013]4001）
