Taxifolin, Extracted from Waste Larix olgensis Roots, Attenuates CCl₄-Induced Liver Fibrosis by Regulating the PI3K/AKT/mTOR and TGF-β1/Smads Signaling Pathways

Abstract

Purpose

Taxifolin is a kind of dihydroflavone and is usually used as a food additive and health food for its antioxidant, anti-inflammatory, and anti-tumor activities. The purpose of this research is to probe into the hepatoprotective activity and the molecular mechanism of taxifolin.

Materials and Methods

The liver fibrosis model was established by intraperitoneal injection of 5 mL/kg body weight of CCl₄ (20% CCl₄ peanut oil solution), and taxifolin was dissolved with 0.9% physiological saline and administered intragastrically to mice.

Results

The results indicated that CCl₄-induced significantly increased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice. Histopathological examination showed severe hepatocyte necrosis and hepatic tissue lesion. Immunohistochemical staining and rt-PCR analysis demonstrated that the expressions of inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, IL-6, and TNF-α were increased. These changes were significantly reversed when treated with taxifolin. In addition, TUNEL staining and Bcl-2/Bax pathway confirmed that taxifolin significantly inhibited hepatocyte apoptosis. Besides, the research confirmed that taxifolin also inhibited the activation of hepatic stellate cells and the production of extracellular matrix (ECM) by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways.

Conclusion

Taxifolin inhibited inflammation, and attenuated CCl₄-induced oxidative stress and cell apoptosis by regulating PI3K/AKT/mTOR and TGF-β1/Smads pathways, which might in part contributed to taxifolin anti-hepatic fibrosis, further demonstrating that taxifolin may be an efficient hepatoprotective agent.

Keywords:

• taxifolin
• liver fibrosis
• PI3K/AKT/mTOR pathway
• TGF-β1/Smads
• inflammation
• apoptosis

Acknowledgments

This work were supported by the National Key Program of the Ministry of Science and Technology of China (No. SQ2020YFF0422819), the Jilin Province Science and Technology Development Project (No. 20200708066YY; No. 20200403166SF) and the Changchun Science and Technology Bureau of Jilin Province (No. 17YJ013).

Disclosure

The authors report no conflicts of interest in this work.