芫花醇提物对不同种属体系UGTs及UGT1A1活性的影响  

Effects of Genkwa Flos Ethanol Extracts on UGTs and UGT1A1 Activities in Different Systems

作　　者：郭嫦娥 苗培培 陈红影 陈宁[1] 马鹏凯[1] 李红品[1] 朱虹宇[1] 高兴[1] 张玉杰[1] GUO Chang-e;MIAO Pei-pei;CHEN Hong-ying;CHEN Ning;MA Peng-kai;LI Hong-pin;ZHU Hong-yu;GAO Xing;ZHANG Yu-jie(School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China)

机构地区：[1]北京中医药大学中药学院,北京100102

出　　处：《中国中医药信息杂志》2017年第4期83-87,共5页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81274177;81073140);北京中医药大学自主选题项目(2016-JYB-XS048;2016-JYB-XS081;2016-JYB-XS058)

摘　　要：目的考察芫花醇提物对UGTs及UGT1A1活性的影响,为阐释芫花毒性机制提供依据。方法采用体外肝微粒体孵育模型,以4-硝基酚为底物检测UGTs活性,以β-雌二醇为底物检测UGT1A1活性,利用UV和HPLC测定底物及代谢物含量。结果芫花醇提物中3种黄酮类成分芹菜素、羟基芫花素、芫花素含量分别为6.34%、8.72%、6.06%,UV测得总二萜含量为31.40%。体外实验表明,在大鼠肝微粒体(RLM)和人肝微粒(HLM)孵育体系中,芫花醇提物均能显著抑制UGTs活性;对UGT1A1活性,在RLM、HLM和重组酶(rh UGT1A1)孵育体系中,芫花醇提物均表现为中等强度的抑制作用,以羟基芫花素计,半数抑制浓度分别为46.32、32.49、8.382μmol/L,抑制类型分别为竞争性抑制作用、反竞争性抑制作用和竞争性抑制作用。结论芫花醇提物对不同肝微粒体孵育体系中UGTs及UGT1A1活性均可产生抑制作用且存在种属差异性,这种抑制作用可能是芫花致肝损伤的机制之一。Objective To investigate the inhibition of Genkwa Flos ethanol extracts on UGTs and UGT1A1activities of different liver microsomes;To predict the toxicity mechanism of Genkwa Flos.Methods By adopting invitro liver microsomes incubation model,4-nitrophenol(4-NP)andβ-estradiol were selected as substrates todetermine activities of UGTs and UGT1A1by UV and HPLC,respectively.Results Content determination resultsshow that there were6.34%of apigenin,8.72%of hydroxygenkwanin and6.06%of genkwanin in ethanol extracts,and total diterpene accounted for31.40%.In vitro research showed that ethanol extracts significantly inhibited UGTsactivity in rat and human liver microsome.UGT1A1activity was inhibited by hydroxygenkwanin with IC50about46.32,32.49and8.382μmol/L in rat liver microsome(RLM),human liver microsome(HLM)and recombinantUGT1A1(rhUGT1A1),respectively.The inhibition types were competitive inhibition in RLM and rhUGT1A1,anduncompetitive inhibition in HLM.Conclusion Ethanol extracts showed different inhibition of UGTs and UGT1A1activities,and the inhibition may reveal one of the mechanisms of liver injury induced by Genkwa Flos.

关 键 词：芫花 醇提物 UGTS UGT1A1 肝微粒体 毒性 抑制作用 

分 类 号：R285.5[医药卫生—中药学]