Effects Of Hesperidin On Liver Fibrosis In Rats And Its Potential Mechanism Involved In The TGF-β/Smad Signaling Pathway

Hepatic fibrosis is regarded as a pathologically repair reaction followed various kinds of chronic liver diseases. It is characterized by an excessive deposition of extracellular matrix proteins(ECM) of which type I collagen predominates. Hepatic fibrosis is a common stage of most chronic liver diseases regardless of the etiology, and its progression may lead to hepatic cirrhosis or hepatocelluar carcinoma(HCC). Although hepatic fibrosis thought to be a reversible pathological state, there is no established effective therapy for hepatic fibrosis yet. Many anti-fibrosis drugs have been developed in recent years. However, no effective anti-fibrotic therapies are available until now. Accordingly, it is significance that understanding the molecular pathophysiology of hepatic fibrosis will lead to novel therapeutic strategies and anti-fibrotic drugs.Hesperidin is a flavonone derivant,by the formative glycoside of Hesperetin and rhamnosidoglucose. Hesperidin is widely present in many kinds of plants and has many pharmacological activities such as anti-inflammatory, antioxidant, anticancer, immunomodulation, the protection of liver and so on.The topic is through to establish the hepatic fibrosis animal model by CCL4 -induced, to get a preliminary understanding the inhibition of HDN on rat hepatic fibrosis. Meanwhile through detect TGF-β/Smad signal transduction Pathway in the key signal transduction mo1ecules TGF-βl, Smad2, Smad3, Smad7, CTGF expression level changes in HSC, to explore HDN the molecular mechanism of anti-fibrosis.1. Protective effects of hesperidin on CCL4-induced liver fibrosis model Rat liver fibrosis was induced by 50% CCL4 twice a week for 12 weeks. From the 7th week, all the therapeutic groups were treated with the HDN(50, 100, 200mg/kg) and the colchicine (0.1mg/kg) respectively for 6 weeks. Compared with the model group, HDN(100, 200mg/kg) not only reduced serum content of ALT, AST, HA, LN, PⅢN P, CIV, TGF-β1 and Hyp, MDA in liver tissue, but also increased SOD activity. Moreover, decreased the TGF-β1, CTGF and procollagenImRNA expression in liver tissues obviously. The results showed that HDN had protective effect on hep- atic fibrosis.2. Effects of HDN on TGF-β/Smad signaling pathway in HSC-T6 cell2.1 Effect of HDN on the proliferation of HSC-T6 cellUsing MTT method based exogenous PDGF-stimulating factor to stimulate HSC-T6 model group. Observing effect of HDN on the proliferation of HSC-T6. The results showed HDN could significantly inhibite the proliferation of HSC, the inhibition rate is proportional to the concentration of HDN.2.2 Effect of HDN on Smad2, Smad3, Smad7mRNA and TGF-β1,CTGF protein expression in HSC-T6 cellPDGF significantly stimulated Smad2, Smad3mRNA and TGF-β1, CTGF protein expression, inbibited Smad7mRNA expression of HSC. HDN treatment could significantly down-regulated Smad2, Smad3mRNA and TGF-β1, CTGF protein expression and up-regulated Smad7mRNA expression.To sum up, HDN has anti-liver fibrosis effect, can be effective in improving liver function, reducing the degree of hepatic fibrosis. Which might be associatedwith the ability to regulate TGF-β/smad signaling pathway.