Quercetin Reduces Hepatic Fibrogenesis by Inhibiting TGF-β/Smad3 Signaling Pathway in LX-2 Cell Line

Background: Liver fibrosis has become one of the leading causes of morbidity and mortality in the world. Liver fibrosis progresses to cirrhosis and can eventually lead to hepatocellular carcinoma (HCC). During fibrogenesis, the hepatic stellate cells (HSCs) remain active and continuously produce more extracellular matrix (ECM). Quercetin, one of the main flavonoids in vegetables, has shown hepatoprotective potential, but its effects on liver fibrosis are not apparent. Objectives: In this study, we investigated the antifibrotic activity of quercetin following stimulation of TGF-beta in the LX-2 cell line (a type of HSC-derived cell line) and its underlying mechanism in vitro. Methods: The LX-2 cells were treated with TGF-beta 1 (2 ng/mL) for 24 h. Next, the cells were treated with quercetin for 24 h, and the mRNA expression of alpha-smooth muscle actin (alpha-SMA), collagen1 alpha 1, and p-Smad3 protein levels were measured. Results: The results showed that the expression of alpha-SMA, collagen 1 alpha 1 (COL1 alpha 1) genes, and also the level of p-Smad3 protein in the presence of TGF-beta increased significantly compared to the control group. Moreover, quercetin in concentrations of 75 and 100 mu M inhibited TGF-beta 1-induced expression of alpha-SMA and COL1 alpha 1 genes and the p-Smad3 protein in LX-2 cells. Conclusions: We conclude that quercetin inhibits further activation of HSCs by inhibiting the TGF-beta/Smad3 signaling pathway and reduces ECM accumulation during liver fibrosis in vitro, and may prevent the progression of liver fibrosis. Thus, the use of quercetin is suggested as a potential therapeutic agent in the treatment of liver fibrosis.