摘要
探讨黄连和黄芩配伍代谢性相互作用的机制。大鼠连续ig黄连、黄芩及药对提取物7 d诱导肝药酶后,采用cocktail探针底物与肝微粒体体外温孵法,通过HPLC同时检测肝微粒体中5种探针底物代谢消除率,评价各给药组对大鼠肝微粒体CYP450酶活性的影响。与空白组相比,黄连对CYP2D6,CYP1A2呈显著抑制作用;黄芩对CYP1A2,CYP2E1,CYP2C9具有显著抑制作用。黄连、黄芩按1∶1配伍后仅对CYP1A2显示抑制作用,对CYP2D6,CYP3A4则呈显著的激活作用;而黄连、黄芩按2∶1配伍后对代谢酶的激活作用消失,表现为对CYP1A2,CYP2C9的显著抑制。结果表明黄连与黄芩对P450酶主要表现为抑制作用,二者按一定比例配伍后作用特点发生改变,呈现出激活和抑制的双重性,且与配伍比例相关。推测黄连与黄芩配伍对代谢酶的抑制和诱导作用是其发挥减毒增效作用的原因之一。
To study the mechanism of metabolic interaction between Coptis chinensis and Scutellaria baicalensis. Rats were giv- en C. chinensis and S. baicalensis for 7 days to produce hepatic microsomal enzyme. Cocktail probe substrate and liver microsome in vitro temperature incubation method were adopted. Meanwhile, the metabolic elimination percentages of the five probe substrates were detected with HPLC, in order to evaluate the effect of each administration group on the enzymatic activity of rat liver microsome CYP450. Compared with the blank group, C. chinensis obviously inhibited CYP2D6 and CYP1A2, and S. baicalensis remarkably in- hibited CYP1A2, CYP2E1 and CYP2C9. The compatibility of C. chinensis and S. baicalensis with the ratio of 1：1 not only inhibited CYP1A2, but also remarkably activated CYP2D6 and CYP3A4. However, their activation effect disappeared under the ratio of 2： 1, and turned into the inhibitory effect on CYP1A2 and CYP＇2C9. The results showed that C. chinensis and S. baicalensis had an inhibitory effect on CYP450, but their compatibility with certain ratio resulted in double effects of activation and inhibition, which was related to their compatibility ratio. It is speculated that the inhibitory and inducing effects of C. chinensis and S. baicalensis on metabolic enzymes are among causes for their attenuation and synergistic effects.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2013年第9期1426-1429,共4页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(30672585
81073140)
北京中医药大学自主选题项目(2011JYBZZ-XS035
2011JYB22X5050)
关键词
黄连
黄芩
配伍
细胞色素P450亚酶
cocktail探针法
鼠肝微粒体
Coptis chinensis
Scutellaria baicalensis
compatibility
cytochrome P450 sub-enzyme
cocktail probe drug ap-proach
rat liver microsome
