Xiaochaihutang attenuates liver fibrosis by activation of Nrf2 pathway in rats

摘要

Graphical abstract Display Omitted Highlights ? XCHT ameliorated CCl 4 -increased serum ALT and AST. ? XCHT decreased CCl 4 -induced elevation of serum LN, HA and PCIII concentrations. ? XCHT treatment alleviated CCl 4 -induced fibrosis pathological changes. ? XCHT decreased α-SMA expression implying the inhibition of the activity of HSCs. ? XCHT increased Nqo-1, HO-1, GCLC and GCLM mRNA and protein levels in the liver. Abstract Xiaochaihutang (XCHT) is a decoction of seven botanical extracts used for liver diseases traditionally in East Asia. However, few studies have investigated its anti-hepatic fibrosis effects and the mechanisms of action. Oxidative stress is one of the key factors responsible for occurrence and development of hepatic fibrosis and nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a major regulator of the cellular defense system against oxidative stress. The aim of the present study was to investigate the effect of XCHT on liver fibrosis and focuse on the Nrf2 pathway in the protection of XCHT against CCl 4 -induced oxidative stress. Liver fibrosis was induced by repeated injection of CCl 4 over a period of 9 weeks. Starting from the 6th week, rats in treatment groups were given the appropriate doses of XCHT granules and Silybin. We discovered that CCl 4 caused significant fibrosis damage in rat liver, and XCHT (5g/kg and 10g/kg, po for 4 weeks) significantly improved the liver functions and fibrosis degree. XCHT treatment significantly decreased the number of α-SMA positive stained cells, indicating suppression of activated hepatic stellate cells (HSCs). Compared with the CCl 4 treatment, administration of XCHT significantly increased the hepatic levels of Nqo1, HO-1, GCLC and GCLM, the major components of the Nrf2 pathway. These studies demonstrated that XCHT is an effective therapeutic agent for treatment of hepatic fibrosis and the mechanism of action might be due to up-regulation of the Nrf2 pathway against oxidative stress, making further inhibition of activated HSCs.