Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT,Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats

摘要

Yu Gan Long(YGL)is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor(TGF-β)in the previous study.But the mechanisms associated with platelet-derived growth factor(PDGF)-BB remain obscure.In this study,we further investigated the mechanism of YGL reducing carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV(Col IV),type HI precollagen(PCHI),hyaluronuc acid(HA)and laminin(LN),which are implicated in liver fibrosis.Also,YGL reduced theα-smooth muscle actin(α-SMA)expression,which acts as the indicator of liver fibrosis.Furthermore,YGL decreased the serum levels of hepatic stellate cell(HSC)mitogen PDGF-BB and inflammation cytokines,including TNF-α,IL-1β,IL-6.Markers involved in liver fibrosis,such as Ras,p-Raf-1,p-ERK1/2,p-JNK,p-P38,p-PI3K,p-AKT,p-JAKl,p-STAT3 were downregulated significantly after treatment with YGL.Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production,and suppressing Ras/ERK,PI3K/AKT,and JAK1/STAT3 signaling pathways,which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL.