Abstract: OBJECTIVE To investigate whether p-hydroxybenzaldehyde (HD),the active ingredient of Nostoc commune,has hepatoprotective efficacy in a high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) rat model and its effect on AMPK/ACC signaling pathway. METHODS Forty-eight SD rats were randomly divided into normal group,model group,silymarin (120 mg·kg^-1) group and HD high,medium and low dose groups (200,100 and 50 mg·kg^-1).Except for the rats in the normal group,which were fed standard chow daily,the rats in all groups were continuously fed high-fat chow for 8 weeks to establish the model.The rats’ body weight,liver coefficients,changes in liver function (ALT,AST),blood lipids (TC,TG,HDL-C,LDL-C),liver antioxidant factors (GSH-Px,SOD,MDA),liver inflammatory factors (TNF-α,IL-6,IL-1β) and other indexes were recorded.HE staining was used to observe the pathological changes of liver tissues,and Western blotting was used to detect the protein expression related to AMPK/ACC signaling pathway.RESULTS Compared with the model group,the body mass and liver coefficients of rats in each dose group of HD and silymarin group were significantly reduced.The results of biochemical indexes showed that HD in the middle and high dose groups significantly reduced serum TC,TG,AST,ALT,LDL-C and MDA levels and increased HDL-C levels in the model rats.ELISA results showed that HD in the middle and high dose groups significantly increased GSH-Px and SOD activities and decreased MDA levels in the liver tissues of NAFLD mice,and significantly reduced the levels of liver inflammatory cytokines TNF-α,IL-6 and IL-1β.HE results showed that HD could significantly reduce hepatic steatosis and inflammatory cell infiltration.Western blotting showed that HD activated AMPK/ACC signaling pathway and significantly increased p-AMPK and p-ACC protein expression in the liver of NAFLD rats.CONCLUSION HD may ameliorate NAFLD by promoting AMPK/ACC signaling pathway to improve hepatic oxidative stress,inflammatory response,and reduce lipid synthesis.