Curcumin protects against CCl4-induced liver fibrosis in rats by inhibiting HIF-1α through an ERK-dependent pathway.

Yanling Zhao,Yan Hu,Xuan He,Xiao Ma,Man Gong,Ruilin Wang,Ping Zhang,Ruisheng Li,Xiaohe Xiao,Shengqiang Luo,Jiabo Wang

doi:10.3390/molecules191118767

Abstract

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1α/ERK pathway in rat liver fibrosis induced by CCl4. In this study, liver fibrosis was induced by CCl4 in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and α-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1α and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1α partly through the ERK pathway.

Highlights

Liver fibrosis is a reversible wound-healing response characterized by the accumulation of extracellular matrix (ECM) following liver injury [1]
We investigated the effect of curcumin on the hepatic stellate cell (HSC) cell line in vitro because HSC plays an important role in liver fibrosis
The results showed that the cell viability of HSC-T6 was significantly reduced from 0.1 to 1.0 μg/mL, demonstrating a remarkable inhibition of HSC proliferation when exposed to curcumin

Summary

Introduction

Liver fibrosis is a reversible wound-healing response characterized by the accumulation of extracellular matrix (ECM) following liver injury [1]. It progresses to cirrhosis, liver failure, and hepatocellular cancer along with fibrogenic development. The end stage of liver fibrosis, is the leading cause of liver-disease-related morbidity and mortality worldwide [2]. Various pathological factors, such as viral hepatitis, alcohol abuse, metabolic diseases, autoimmune diseases, and cholestatic liver diseases, all contribute to the development of liver fibrosis [3]. The activated HSC causes the progressive ECM synthesis rather than degradation, resulting in accumulation of ECM, which leads to liver fibrosis [5]

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