Taxifolin, Extracted from Waste Larix olgensis Roots, Attenuates CCl4-Induced Liver Fibrosis by Regulating the PI3K/AKT/mTOR and TGF-β1/Smads Signaling Pathways
Authors Liu X, Liu W, Ding C, Zhao Y, Chen X, Ling D, Zheng Y, Cheng Z
Received 11 September 2020
Accepted for publication 21 December 2020
Published 26 February 2021 Volume 2021:15 Pages 871—887
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Manfred Ogris
Xinglong Liu,1 Wencong Liu,1,2 Chuanbo Ding,1 Yingchun Zhao,1 Xueyan Chen,1 Dong Ling,1 Yinan Zheng,1 Zhiqiang Cheng3
1College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, People’s Republic of China; 2State Local Joint Engineering Research Center of Ginseng Breeding and Application, Changchun 130118, People’s Republic of China; 3College of Resources and Environment, Jilin Agricultural University, Changchun 130118, People’s Republic of China
Correspondence: Wencong Liu
College of Resources and Environment, Jilin Agricultural University, #2888 Xincheng Street, Changchun 130118, People’s Republic of China
Tel +86 138 0446 0499
Email [email protected]
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-β 1/Smads pathways.
Conclusion: Taxifolin inhibited inflammation, and attenuated CCl4-induced oxidative stress and cell apoptosis by regulating PI3K/AKT/mTOR and TGF-β 1/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-β 1/Smads, inflammation, apoptosis
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]