Resveratrol Alleviates Hepatic Fibrosis in Associated with Decreased Endoplasmic Reticulum Stress-Mediated Apoptosis and Inflammation
Zhenyu Ma, Lulu Sheng, Juan Li, Jianmin Qian, Gang Wu, Zhengxin Wang, Yi Zhang
Abstract
Abstract — Hepatic fibrosis (HF) is the typical response to chronic liver disease and is characterized by deposition of abundant extracellular matrix. The aim of the present study was to investigate the protective effect of resveratrol (RSV) in a CCl 4 -induced rat model of HF. We demonstrate that the administration of RSV effectively improves liver function and ameliorates liver fibrosis by reducing collagen deposition and reversing the expression of COL1A1 and PPAR-γ. Treatment efficacy of RSV could be attributed to reversed epithelial-mesenchymal transition progress with upregulated expression of E-cadherin and downregulated N-cadherin, vimentin, and α-SMA. Moreover, RSV significantly decreased the levels of endoplasmic reticulum stress (ERS)-related proteins CHOP; Bip; cleaved caspase-3, caspase-7, and caspase-12; Bax; and Bak while promotes the expression of anti-apoptosis protein Bcl2. The important role of ERS in HF was confirmed by using 4-PBA, an ERS inhibitor, which markedly ameliorated CCl 4 -induced HF. Further, mechanistic studies demonstrated that RSV significantly decreased CCl 4 -induced transforming growth factor-β synthesis and inflammatory factor (tumor necrosis factor-α and interleukin-6) expression and reduced the inflammation of hepatic stellate cells by inhibiting the NF-κB pathway in vivo and in vitro . In conclusion, the results suggested that RSV ameliorated HF in associated with decreased ERS-induced apoptosis and inflammation in rats.