Aloperine Alleviates Ethanol Acute Exposure-Evoked Hepatocyte Injury By Restraining Oxidative Stress Through The Nrf2-Ho-1 Axis

Alcoholic liver injury caused by acute or chronic alcohol consumption constitutes the second largest liver disorder after viral hepatitis. Emerging evidence confirms the therapeutic potential of aloperine in several injury-related diseases. Nevertheless, its function in acute alcoholic live injury remains ill-defined. In this research, aloperine treatment exhibited little cytotoxicity in mouse hepatocytes. Importantly, aloperine afforded cytoprotective effects against acute ethanol exposure-induced cell injury by enhancing cell viability, proliferation-related marker PCNA expression and suppressing cell apoptosis and caspase-3 activity. Moreover, aloperine restrained the oxidative stress response evoked by ethanol in hepatocytes by decreasing ethanol-increased ROS generation, lactate dehydrogenase (LDH) and malondialdehyde (MDA) leakages, but elevating antioxidant stress superoxide dismutase (SOD) and glutathione (GSH) levels. Additionally, the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) induced by acute ethanol exposure were reduced following aloperine treatment. Mechanistically, aloperine enhanced activation of the Nrf2-HO-1 signaling by increasing protein expression of Nrf2, HO-1, Bcl-2 and decreasing pro-apoptotic Bax protein levels. Noticeably, blocking this pathway offset aloperine-mediated hepato-protective efficacy and anti-oxidative stress response. Together, these findings highlight that aloperine may protect against acute ethanol-induced cytotoxic injury in hepatocytes by inhibiting oxidative stress via activation of the Nrf2-HO-1 axis, implying a promising potential for aloperine against ethanol-induced acute liver disease.