HIMH0021 attenuates ethanol-induced liver injury and steatosis in mice

Chronic alcohol consumption causes alcohol-induced lipogenesis and promotes hepatic injury by preventing the oxidation of hepatocellular fatty acids through the suppression of the activation of AMP-activated protein kinase (AMPK). HIMH0021, an active flavonoid compound, which is a component of the Acer tegmentosum extract, has been shown to protect against liver damage caused by alcohol consumption. Therefore, in this study, we aimed to determine whether HIMH0021 could regulate alcoholic fatty liver and liver injury in mice. Oral administration of 10 days of Lieber-DeCarli ethanol plus a single binge of 30% ethanol (chronic-plus-binge model) induced steatosis and liver injury and inflammation in mice, which appears similar to the condition observed in human patients with alcohol-related diseases. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1 alpha. These findings suggested that HIMH0021 could be used to target a TNF alpha-related pathway for treating patients with alcoholic hepatitis.