The alleviating effect of quercetin on carbon tetrachloride-induced liver fibrosis in rats and its underlying mechanism

doi:10.5246/jcps.2022.11.071

Abstract

Abstract:

Quercetin, a phenolic phytochemical widely present in vegetables and fruits, has antioxidant, anti-inflammatory, antiviral, and immunomodulatory activities, and it has been successfully used in the treatment of acute and chronic diseases. In the present study, we aimed to investigate the alleviation effect of quercetin on rat liver fibrosis and explore its mechanism of action. Healthy male SD rats were randomly divided into the normal group, model group, and quercetin group, with six rats in each group. Liver fibrosis was induced by intraperitoneal injection of 1 mL/kg carbon tetrachloride (50% v/v in olive oil) twice a week for 6 weeks, and quercetin (100 mg/kg/d) was administered orally in the 7th week until the end of the 12th week. Blood and liver samples were collected at 1 h after the last administration. Serum liver function parameters (AST, ALT, ALP, GGT, and TBA) were detected by an automatic biochemical analyzer. H&E, Masson, and Sirius red staining were used to observe the pathological morphology of liver tissue. Western blotting analysis was used to evaluate the expressions of liver fibrotic factors (TGF-β1, α-SMA, MMP2, and MMP9) and bile acid-related regulatory proteins (FXR, CYP7A1, CYP8B1, and CYP27A1). The oxidative stress markers (GSH, GSH-Px, GR, SOD, and MDA) in the liver tissue were detected using corresponding kits. The contents of bile acids in the liver tissue were determined by LC-MS/MS. The results showed that compared with the model group, quercetin treatment could significantly reduce serum AST, ALT, and TBA levels (P < 0.05). The fibrotic liver injury was significantly improved, and the expressions of fibrotic factors TGF-β1, α-SMA, MMP2, and MMP9 were significantly decreased (P < 0.05). Liver GSH, GSH-Px, GR, and SOD levels were significantly increased (P < 0.05), and the MDA level was significantly decreased (P < 0.05). The contents of hepatic bile acids were significantly decreased (P < 0.05), the expression of FXR was significantly increased (P < 0.05), and the expressions of CYP7A1 and CYP8B1 were significantly decreased (P < 0.05). This study suggested that quercetin could effectively alleviate carbon tetrachloride-induced liver fibrosis injury, and its mechanism of action was related to improving the liver’s ability to resist oxidative stress and reducing the expressions of fibrotic factors and bile acid synthesis.

Key words: Quercetin, Liver fibrosis, Carbon tetrachloride, Oxidative stress, Fibrosis cytokines, Bile acids

Supporting:

Mingkang Zhang, Yuyue Chen, Yan Zhou, Xin'an Wu. The alleviating effect of quercetin on carbon tetrachloride-induced liver fibrosis in rats and its underlying mechanism[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(11): 840-852.

Figures/Tables 7

Table 1. LC-MS/MS analysis methods of bile acids.

Table 2. The effect of quercetin on serum biochemical parameters.

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