Nuciferine alleviates acute alcohol-induced liver injury in mice: Roles of suppressing hepatic oxidative stress and inflammation via modulating miR-144/Nrf2/HO-1 cascade

Abstract

Binge consumption of alcohol results in severe global health problem. This study aimed to explore the potential efficacy of nuciferine (NCF) in protecting acute alcohol-induced liver injury and the underlying molecular mechanisms. We revealed that NCF activated Nrf2/HO-1 signaling in HepG2 hepatocytes and relieved alcohol-induced ROS generation and subsequent cell death. Mechanistically, suppression of miR-144 expression contributed to NCF-mediated activation of Nrf2/HO-1 signaling. Consistently, NCF modulated hepatic miR-144/Nrf2/HO-1 axis and alleviated acute alcohol-induced liver injury as well as concomitant oxidative stress and inflammation in mice. In addition, suppressing the catalytic activity of HO-1 by ZnPP, an inhibitor of HO-1, diminished the hepatoprotective effects of NCF. The ameliorative effects of NCF on acute alcohol-provoked hepatic oxidative stress and inflammation were also crippled by ZnPP. Taken together, our data suggested that NCF is able to relive acute alcohol-induced liver injury and modulating miR-144/Nrf2/HO-1 cascade is implicated in the hepatoprotective activity of NCF.

Keywords

• Nuciferine
• Acute alcohol-induced liver injury
• Nrf2/HO-1 pathway
• MiR-144