3种中药成分对CYP2C9酶的影响

Effects of Quercetin, Paeoniflorin and Oleanolic Acid on CYP2C9 Activities in Vitro

目的评价槲皮素、芍药苷、齐墩果酸对CYP2C9酶活性的抑制作用,为临床合理用药提供参考。方法利用大鼠肝微粒体,以甲苯磺丁脲作为评价CYP2C9活性的体外探针,以高效液相色谱法测定代谢产物羟基甲苯磺丁脲生成量,评价槲皮素、芍药苷、齐墩果酸对CYP2C9酶的抑制作用。以磺胺苯吡唑为阳性对照,分别计算槲皮素、芍药苷、齐墩果酸的抑制率,绘制抑制曲线并计算半数抑制浓度(IC_(50)值)。结果 3种中药成分对CYP2C9均有一定的抑制作用,槲皮素、芍药苷、齐墩果酸IC_(50)分别为15.343,49.361,4.115μmol·L^(-1),其中齐墩果酸的抑制作用最强,而芍药苷作用效果不明显。结论齐墩果酸可中等强度抑制CYP2C9酶活性,而槲皮素和芍药苷的酶活性抑制作用较弱。

Objective To investigate the effects of quercetin, paeoniflorin and oleanolic acid on the activities of CYP2 C9 enzymes in vitro for clinical combination therapy. Methods Tolbutamide served as in vitro probes to evaluate CYP2 C9 activity in liver microsome. HPLC method was used to detect themetabolites,hydroxytoluene sulfobutamide production and to evaluate the effects of quercetin, paeoniflorin and oleanolic acid on the activities of CYP2 C9 enzymes. Inhibition rate and IC50 of quercetin, paeoniflorin and oleanolic acid were calculated with sulfaphenazole as positive control. Results Among the 3 active constituents tested, oleanolic acid was found to be a moderate inhibitor on CYP2 C9 with IC50 of 4.115 μmol·L-1. Quercetin and paeoniflorin was a poor inhibitor for CYP2 C9 with IC50 of 15.343 and 49.361 μmol·L-1, respectively. Conclusion Oleanolic acid is a moderate inhibitor of CYP2 C9, while quercetin, paeoniflorinweakly suppresses the activity of CYP2 C9.