Abstract
BackgroundCirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process.MethodsCirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α.ResultsBoth YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.ConclusionsYGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.
Highlights
Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture
We previously reported that YGJ exerts therapeutic effects on carbon tetrachloride (CCl4)-induced cirrhosis in rats, by inhibiting hepatocyte apoptosis and hepatic stellate cell (HSC) activation, as well as regulating the function of Kupffer cells [7]
YGJ and Ingredients of YGJ (iYGJ) against Carbon tetrachloride (CCl4)-induced cirrhosis At the end of the 6th week, serum alanine transaminase (ALT) and Aspartate aminotransferase (AST) activity were significantly higher in the CCl4 model group than in controls (P < 0.05)
Summary
Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process. Yiguanjian (YGJ) decoction was first described in ancient traditional Chinese medicine and has been used to treat hepatic diseases in China for centuries. Research indicates that hepatoprotective and anti-fibrogenic effects of YGJ against dimethylnitrosamine (DMN)-induced hepatic injury. We previously reported that YGJ exerts therapeutic effects on carbon tetrachloride (CCl4)-induced cirrhosis in rats, by inhibiting hepatocyte apoptosis and hepatic stellate cell (HSC) activation, as well as regulating the function of Kupffer cells [7]. Modified YGJ induced HSC apoptosis via reactive oxygen species accumulation and inducing the intrinsic apoptotic pathway in vitro [8]. We investigated the effects of YGJ and iYGJ on angiogenesis and studied the mechanisms underlying this process
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