Paeonol alleviated acute alcohol-induced liver injury via SIRT1/Nrf2/NF-κB signaling pathway

Abstract

In this study, the beneficial effect of paeonol on acute alcohol-induced liver injury and the basic mechanisms were investigated. in vitro, HepG2 cells were treated with paeonol for 24 h before it were exposed to alcohol for 24 h. in vivo, male C57BL/6 mice were used to establish alcohol-induced liver injury models by oral gavage of alcohol (5 g/kg BW). Paeonol pretreatment showed statistically significant reduction in alcohol-induced ROS, MDA, IL-1β, IL-6, TNF-α, and nitric oxide, while GSH content was retained (P < 0.05). Furthermore, paeonol treatment resulted in the increase of Nrf2 nuclear translocation, the increase of NQO-1 and HO-1 expression, and the suppression of NF-κB p65 nuclear translocation. However, pretreatment with NAM (inhibitor of SIRT1) not only inhibited the effect of paeonol on reducing nuclear translocation of NF-κBp65, but also inhibited the effect of paeonol on promoting the expression of nuclear Nrf2, NQO1 and HO-1. Besides, paeonol pretreatment at test doses significantly ameliorated alcohol-induced edema, hepatocyte necrosis and hepatic cord irregular. These results demonstrated that paeonol has the high potential for relieving acute alcohol-induced liver injury.

Keywords: Alcoholic liver disease; Inflammation; Oxidative stress; Paeonol; SIRT1.