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Int J Biol Sci 2019; 15(4):788-799. doi:10.7150/ijbs.30677

Research Paper

Farrerol Ameliorates APAP-induced Hepatotoxicity via Activation of Nrf2 and Autophagy

Lidong Wang, Wei Wei, Qingfei Xiao, Huahong Yang, Xinxin Ci

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130001, China

Abstract

Farrerol has been shown to have antioxidative potential via Nrf2 activation, which in turn is involved in the prevention of hepatotoxicity. The purpose of the current study was to explore the protective effect of farrerol against acetaminophen-induced hepatotoxicity and its underlying mechanisms. Mice were used to evaluate the hepatoprotective effect of farrerol on liver injury induced by acetaminophen in vivo. HepG2 cells were utilized to further determine the functional role and mechanisms by which Nrf2 and autophagy are involved in the hepatoprotective effect of farrerol in vitro. We found that treatment with farrerol leads to a significant reduction in acetaminophen-induced hepatotoxicity by decreasing mortality, histopathological liver changes, and ALT and AST levels. Furthermore, farrerol effectively suppressed mitochondrial dysfunction by reducing JNK phosphorylation, Bax mitochondrial translocation, AIF and cytochrome c release. Further investigations revealed that the activation of Nrf2 and the induction of autophagy via the AMPK/AKT pathway by farrerol contributed to its hepatoprotective activity in vitro. In addition, farrerol inhibited acetaminophen-induced the mortality and histopathological changes in WT mice were evidently alleviated but not abrogated in Nrf2 -/- mice, which attributed to the induction of autophagy. Together, farrerol has protective potential against acetaminophen-induced hepatotoxicity which may be associated with activation of Nrf2 and autophagy.

Keywords: Farrerol, APAP, Hepatotoxicity, Nrf2, Autophagy

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Wang L, Wei W, Xiao Q, Yang H, Ci X. Farrerol Ameliorates APAP-induced Hepatotoxicity via Activation of Nrf2 and Autophagy. Int J Biol Sci 2019; 15(4):788-799. doi:10.7150/ijbs.30677. Available from http://www.ijbs.com/v15p0788.htm