Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE:Xuefuzhuyu decoction (XFZY) is a well-known traditional Chinese herbal formulation composed of 11 herbs. It is an effective treatment for cardiovascular and chronic liver diseases. The aim of the study is to investigate the role of XFZY on angiogensis in hepatic fibrogenesis, and identify the possible mechanism. MATERIAL AND METHODS:Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl₄) in C57BL/6 mice for 6 weeks. From week 4 to week 6, the CCl₄-injected mice were randomly divided into three groups, followed by oral administration of Sorafenib, XFZY and water for 3 weeks. Biochemical parameters, hydroxyproline (Hyp) content and histological changes of the liver were determined. The expressions of alpha smooth muscle actin (α-SMA), collagen I, CD31 and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and western blot. The protein expressions of VEGFR-2, hypoxia inducing factor (HIF)-1α, asymmetric dimethylarginine (ADMA) and dimethylarginine hydrolase (DDAH) 1 were determined by western blot. The mRNA levels of α-SMA, VEGF and HIF-1α were measured by RT-PCR. RESULTS:Both Sorafenib and XFZY improved biochemical parameters of the liver fibrosis mice. A significant reduction in Hyp content was found in the XFZY-treated mice as well as the Sorafenib-treated mice. Changes in histopathology showed that Sorafenib and XFZY decreased inflammatory and fibrotic stages of the liver in fibrosis mice. Compared to CCl4 model group, Sorafenib and XFZY decreased α-SMA, collagen I, CD31, VEGF, VEGFR-2, HIF-1α and ADMA, and increased the expression of DDAH1. CONCLUSION:XFZY inhibits liver fibrosis not only through inhibiting collagen deposition but also through an antiangiogenic effect on the fibrotic liver. Moreover, the antiangiogenic mechanism of XFZY involves alleviating hypoxia and protecting liver sinusoidal endothelial cell function.
journal_name
J Ethnopharmacoljournal_title
Journal of ethnopharmacologyauthors
Zhou YN,Sun MY,Mu YP,Yang T,Ning BB,Ren S,Chen JM,Liu Pdoi
10.1016/j.jep.2014.03.019subject
Has Abstractpub_date
2014-05-14 00:00:00pages
659-66issue
3eissn
0378-8741issn
1872-7573pii
S0378-8741(14)00196-2journal_volume
153pub_type
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