Xiaochaihutang attenuates liver fibrosis in rats through activation of Nrf2 pathway

Jin LI,Rui HU,Shang-fu XU,Yuan-yang LI,Jie LIU,Ying QIN,Zhi XIAO

(Zunyi Medical University,1.Research Center for Medicine&Biology,2.Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi 563003,China)

T2-6

Xiaochaihutang attenuates liver fibrosis in rats through activation of Nrf2 pathway

Jin LI1,Rui HU1,Shang-fu XU2,Yuan-yang LI1,Jie LIU2,Ying QIN1,Zhi XIAO1

(Zunyi Medical University,1.Research Center for Medicine&Biology,2.Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi 563003,China)

OBJECTIVEOxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related factor 2(Nrf2)serves as a major regulator of a cellular defense system against oxidative stress.Xiaochaihutang(XCHT),a compound of seven botanical extracts used for liver diseases traditionally in East Asia.However,few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action.The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway.METHODSLiver fibrosis was induced by repeated injection of Carbon tetrachloride(CCl4)over a period of 9 weeks.Starting from the 6thweek,the animals in treatment groups were given the appropriate dose of XCHT granules and silybin.Biochemical parameters,histological changes of the liver and alpha-smooth muscle actin(α-SMA)were determined.The expressions of Nrf2,Keap1,Nqo1,HO-1,Gclc and Gclm were assessed by RT-PCR and Western blot.RESULTSCCl4caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT(5 g·kg-1and 10 g·kg-1).XCHT(5 g·kg-1and 10 g·kg-1)treatment significantly decreased the number of cells labeled with α-SMA antibodies.Moreover,XCHT(5 g·kg-1and 10 g·kg-1)significantly increase Nqo1,HO-1,Gclc and Gclm expressions in the liver.CONCLUSIONThese studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress,making further efforts to inhibiting the activated HSCs.Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.

Xiaochaihutang;liver fibrosis;Nrf2 pathway