金银花提取物及主要成分对药物代谢酶CYP3A4的活性抑制作用研究

Study on the Inhibition of Drug Metabolizing Enzyme(CYP3A4)Activity by Honeysuckle Extract and its Main Components

目的:考察金银花提取物及其主要成分绿原酸、咖啡酸和芦丁对CYP3A4活性的抑制作用。方法:采用重组人CYP3A4孵育法,以咪达唑仑作为该酶的活性探针药物,采用液相色谱-质谱联用法(LC-MS/MS)测定代谢产物1′-羟基咪达唑仑的浓度,计算代谢产物的初始生成速度,比较加入待测药物和空白对照时代谢产物的初始生成速度。结果:金银花提取物、绿原酸、芦丁对该酶有抑制作用,IC50值分别为2.13mg/mL、28.8μmol/L和17.6μmol/L,且金银花提取物和绿原酸对该酶的抑制作用不可逆,咖啡酸的抑制作用很弱,几乎不会导致药物相互作用。结论:金银花可能影响联合使用的CYP3A4的底物药物的代谢。

Objective：To study on the inhibition of CYP3A4 activity by honeysuckle extract as well as three main components （chlorogenic acid, caffeic acid and rutin）. Methods：Incubation experiment of recombinant human CYP3A4 was carried out to assay the activities of enzymes. Midazolam was used as the active probe of the enzyme. After incubation, concentration of the metabolite l′-hydroxymidazolam was quantified by LC-MS/MS. The initial formation rates of metabolites were calculated and the formation velocities of metabolites were compared with or without the analyte. Results：The honeysuckle extract as well as chlorogenic acid and rutin showed obvious inhibitory effects on the five enzymes with IC50 values of 2.13 mg/mL, 28.8 μmol/L and 17.6 μmol/L, respectively. Also, the inhibitory effects of honeysuckle extract and chlorogenic acid on the enzymes were irreversible. Conclusion：It was indicated that honeysuckle may affect the metabolism of the jointly used CYP3A4 substrates.