6-O-galloylsalidroside, an active ingredient from Acer tegmentosum, ameliorates alcoholic steatosis and liver injury in a mouse model of chronic ethanol consumption

Abstract

We previously reported that Acer tegmentosum extract, which is traditionally used to treat liver disease in Korea, may help reduce fat accumulation, improve liver metabolism, and suppress inflammation in alcoholic liver disease. The active ingredient was found to be 6-O-galloylsalidroside, which was isolated from the methanol extract of A. tegmentosum. We hypothesized that 6-O-galloylsalidroside extracted from A. tegmentosum may help protect from liver damage and attenuate hepatic fat accumulation associated with chronic alcohol consumption. In the present study, we aimed to investigate whether 6-O-galloylsalidroside can regulate alcoholic fatty liver and liver injury in mice. For this purpose, mice were fed with Lieber-DeCarli 5% ethanol diet for 11 days to induce steatosis and liver injury. Oral 6-O-galloylsalidroside was administered once a day for 11 days. Intrahepatic lipid accumulation caused by alcohol consumption was measured using in vivo 1H magnetic resonance imaging. Hepatic steatosis was observed histologically in tissue samples stained with hematoxylin and eosin, as well as Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, as well as the triglyceride content in liver homogenates. On magnetic resonance spectroscopy, 6-O-galloylsalidroside appeared to alleviate alcohol-induced steatosis, which was reflected in decreased hepatic and serum triglyceride levels despite ethanol feeding. Furthermore, 6-O-galloylsalidroside treatment was associated with decreased RNA expression of Cd36, which plays an important role in the development of alcoholic steatosis through the hepatic de novo lipogenesis pathway. Furthermore, treatment with 6-O-galloylsalidroside inhibited the expression of cytochrome P4502E1 and attenuated hepatocellular damage, reflected in reduced ALT and AST levels. These findings suggest that 6-O-galloylsalidroside extracted from A. tegmentosum might serve as a bioactive agent for treating alcoholic fatty liver and liver damage.