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

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.

In this study, we investigated the antifibrotic activity of quercetin following stimulation of TGF-β in the LX-2 cell line (a type of HSC-derived cell line) and its underlying mechanism in vitro.

The LX-2 cells were treated with TGF-β1 (2 ng/mL) for 24 h. Next, the cells were treated with quercetin for 24 h, and the mRNA expression of α-smooth muscle actin (α-SMA), collagen1α1, and p-Smad3 protein levels were measured.

The results showed that the expression of α-SMA, collagen 1α1 (COL1α1) genes, and also the level of p-Smad3 protein in the presence of TGF-β increased significantly compared to the control group. Moreover, quercetin in concentrations of 75 and 100 µM inhibited TGF-β1-induced expression of α-SMA and COL1α1 genes and the p-Smad3 protein in LX-2 cells.

We conclude that quercetin inhibits further activation of HSCs by inhibiting the TGF-β/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.