6种中药提取物体外对大鼠肝细胞色素CYP450活性的影响  

Effects of six kinds of Chinese herb extracts on the activities of rat liver microsomes in vitro

作　　者：毕云枫[1,2] 朱洪彬[2] 邢俊鹏[2] 刘志强[2] 宋凤瑞[2] 

机构地区：[1]吉林农业大学食品科学与工程学院,吉林长春130118 [2]中国科学院长春应用化学研究所,化学生物学实验室&长春质谱中心,吉林长春130022

出　　处：《药学学报》2013年第7期1131-1135,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81073040);国家博士后基金资助项目(2011M500625)

摘　　要：利用UPLC-MS/MS的多反应监测(MRM)技术,结合多探针底物方法,对6种中药提取物——山楂叶提取物、淫羊藿提取物、刺五加叶提取物、红车轴草提取物、银杏叶提取物和葛根提取物对细胞色素亚型CYP1A2、CYP2C、CYP2E1、CYP2D和CYP3A的活性影响进行了系统研究。结果表明,6种提取物对各CYP亚型酶均有抑制能力,其中山楂叶提取物对CYP2D的抑制能力最强,IC50值仅为4.04μg.mL 1;红车轴草提取物对CYP2D的抑制能力也较强,其IC50值为5.73μg.mL 1;山楂叶提取物对CYP2E1也有较强的抑制能力,IC50值为10.91μg.mL 1。此外,银杏叶提取物对CYP3A、2D、2E1的IC50值分别为45.12、35.45和22.41μg.mL 1,刺五加叶提取物对CYP2E1抑制的IC50值为32.89μg.mL 1。机理性抑制实验结果表明,山楂叶提取物和葛根提取物对CYP2E1和CYP2D的抑制随着预孵时间延长而增强。Effects of six kinds of Chinese herb extracts, including Folium Crataegi extract, Herba Epimedii extract, Folium Acanthopanacis Senticosi extract, Trifolium pratense L. extract, Folium Ginkgo extract and Radix Puerariae extract, on the activities of CYP450 isozymes （CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A） in rat hepatic microsomals Were studied by using a UPLC-MS/MS （MRM） and cocktail probe substrates method. The results showed that effects of six kinds of Chinese herb extracts on each CYP450 isozyme activity were inhibitory. The IC50 of Folium Crataegi extract for the inhibition of rat microsomal CYP2D activity was only for 4.04 μg·mL^-1, which showed the highest inhibition; Trifolium pratense L. extract had strong inhibitory action to CYP2D, the IC50 value was 5.73 μg·mL^-1; Folium Crataegi extract also had strong inhibitory action on CYP2E1, the IC50 value was 10.91 μg·mL^-1. Furthermore, the IC50 of Folium Ginkgo extract for the inhibition of rat microsomal CYP3A, 2D, 2El activities were 45.12, 35.45 and 22.41 μg·mL^-1, respectively, and the IC50 of Folium Acanthopanacis Senticosi extract on the inhibition of rat microsomal CYP2E1 activity was 32.89 μg·mL^-1. In addition, mechanism of inhibition experimental results showed that the inhibiting abilities of Folium Crataegi extract and Radix Puerariae extract on each CYP450 isozyme increased with the increasing of the preincubation time, therefore, the inhibitory effects were a mechanism-based inhibition.

关 键 词：中药提取物 CYP450 UPLC-MS MS 

分 类 号：R968[医药卫生—药理学]