Plumbagin Ameliorates CCl 4 -Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway.

Si Chen,Jin-Guo Wang,Da-Zhi Chen,Yi-Jing Cai,Bi Chen,Yao-Ren Hu,Zhuo Lin,Li-Yun Fu,Yi Chen,Yong-Ping Chen,Xiao-Dong Wang,Zhuo-Lin Zou

doi:10.1155/2015/645727

Abstract

Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4 treated rats. At concentrations of 2 to 6 μM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF-like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression of α-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells.

Highlights

Liver fibrosis is a wound-healing response to chronic liver injuries associated with various etiologies including viral, metabolic, genetic, and cholestatic liver disease [1]
(2) Alcoholic liver disease can be mimicked by ethanol [11] and NAFLD can be mimicked by choline-deficient, Lamino acid-defined, methionine-deficient diet and high-fat diet administrated on the animals [12,13,14,15]
When fibrosis score was evaluated in liver sections by Semiquantitative Scoring System (Figure 2(a)), significantly higher histological fibrosis score was found in the CCl4 group compared to control group (P < 0.05)

Summary

Introduction

Liver fibrosis is a wound-healing response to chronic liver injuries associated with various etiologies including viral, metabolic, genetic, and cholestatic liver disease [1]. (3) Immunogens including plant protein concanavalin A and xenogeneic serum cause allergic reaction and inflammation, stimulating fibrosis formation [16, 17]. A variety of animal models mimic different pathogeny (viral hepatitis, alcoholic liver disease, NAFLD, autoimmune liver diseases, cholestasis, etc.) induced liver fibrosis and cirrhosis in mice, rats, rabbits, and pigs [7]. Those approaches mimic the process of autoimmune liver diseases provoking liver fibrosis. Those approaches mimic the process of autoimmune liver diseases provoking liver fibrosis. (4) An operation of bile duct ligation is used as the animal

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Discussion

Conclusion