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1. Introduction
Liver fibrosis is caused by severe liver damage that occurs in many patients with liver injury such as persistent viral and helminthic infections, overuse of alcohol or nonalcoholic steatohepatitis (NASH), autoimmunity, drug intoxication, and some hereditary disease [1, 2]. Hepatic stellate cell (HSC) proliferation and activation are thought to be crucial for the progression of liver fibrosis [3]; HSCs change from a quiescent status to activation and undergo transformation into myofibroblast-like cells which produce excessive extracellular matrix (ECM) proteins including α-smooth muscle actin (α-SMA) and type I collagen. Excessive depositions of these ECM proteins in liver tissue result in fibrogenesis and disturb matrix degradation that causes the loss of homeostasis in liver tissue followed by progression to liver cirrhosis and hepatocellular carcinoma [4, 5].
Recent studies reveal that liver fibrosis and cirrhosis is a reversible process [6, 7]. Removal of the liver injury-causing factors followed by a decrease in proinflammatory cytokines and an induction of activated HSC apoptosis may cause liver fibrosis diminution [8]. Therefore, suppression of HSC activation and proliferation and induction of apoptosis in activated HSCs have been proposed as therapeutic strategies for the treatment and prevention of hepatic fibrosis [1, 9, 10].
Yi Guan Jian (YGJ) decoction consists of six kinds of Chinese herbs and is a traditional Chinese hepato-therapeutic herbal formula. According to the Chinese medicine theory, the modified Yi Guan Jian (mYGJ) is formulated by adding three more herbs including Astragalus membranaceus, Trionyx sinensis Wiegmann (Carapax Trionycis), and Eupolyphaga sinensis Walker into the original YGJ to activate blood and resolve stasis, tonifies qi, and hard mass for the patients with liver diseases. Although there is still no evidence-based clinical study, YGJ has shown apparent efficacy in outpatients with chronic liver diseases such as fibrosis and cirrhosis to improve clinical symptoms, liver function, and quality of life for patients. Besides, the major active components of YGJ extract, ferulic acid and catalpol, significantly inhibit the progression of hepatic fibrosis in carbon tetrachloride-induced animal model study [11]. However, the underlying mechanism for the antifibrotic effects of YGJ or mYGJ is still unclear. In this study, we demonstrate that mYGJ inhibits HSC-T6 hepatic stellate cell proliferation concomitant with a significant decrease in the expression of liver fibrosis marker