Therapeutic Effects of Yinchenhao Decoction on Alpha-naphthylisothiocyanate Induced Intrahepatic Cholestasis in Rats
Yinchenhao Decoction(YCHD),a famous traditional Chinese formula,has been used for treating cholestasis for thousands of years.Its cholagogic effect has been widely reported,but its pharmacodynamic material and underlying therapeutic mechanism remain unclear.By using UHPLC-Q/TOF,eleven original active components and eight phase Ⅱ metabolites were detected in rats after oral administration of YCHD,including three new phase Ⅱ metabolites.And it indicated that phase Ⅱ metabolism was one of the major metabolic pathway for most active components in YCHD,which was similar to the metabolism process of bilirubin.It arouses our curiosity that whether the metabolism process of YCHD has any relationship with its cholagogic effects.So a new method for simultaneous quantitation of 8 active components and 4 phase Ⅱmetabolites of rhein,emodin,genipin,and capillarisin has been developed and applied for their pharmacokinetic study in both normal and alpha-naphthylisothiocyanate(ANIT)-induced intrahepatic cholestasis rats.The pharmacokinetic behaviors of most components of YCHD were inhibited,which was hypothesized to be related to different levels of metabolic enzymes and transporters in rat liver.So dynamic changes of intrahepatic enzyme expression in cholestasis and YCHD treated rats have been monitored by an UHPLC-MS/MS method.The results showed expression levels of UGT1A1,OATP1A4,MRP2 were significantly inhibited in cholestasis rats,which would account for reducing the drug absorption and the metabolic process of YCHD in cholestatic rats.A high dose(12 g/kg)of YCHD remarkably increased the expression of UGT1A1,bile salt export pump,MRP2,OATP1A4 in cholestasis rats presented it exhibited the greatest therapeutic effect on cholestasis.Considering the metabolic process of bilirubin in vivo,the choleretic effect of YCHD is proven to be related to its regulatory action on expression of metabolic enzymes and transporters in cholestatic liver.
Yinchenhao Decoction phase Ⅱ metabolism pharmacokinetics cholestasis bilirubin metabolism enzyme metabolic transporter Introduction
Yue Ding Ya-Xiong Yi Tong Zhang
School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai,China,201203 Experiment Center for Teaching and Learning,Shanghai University of Traditional Chinese Medicine,Shan
国内会议
江西赣州
英文
392-413
2018-08-01（万方平台首次上网日期，不代表论文的发表时间）