Protective Effect Of P-Hydroxybenzaldehyde On Nonalcoholic Fatty Liver In Rats

Objective: The target and key pathway of HD treatment for NAFLD were predicted by network pharmacological analysis.A confirmatory experiment was conducted to explore whether the active component of Nostoc commune has the hepatoprotective effect of hydroxybenzaldehyde(HD)on the rat model of high-fat diet-induced non-alcoholic fatty liver(NAFLD)and its effect on AMPK/ACC signaling pathway,providing new clinical treatment ideas.Methods: Using databases such as Swiss Target Prediction to search for effective active ingredients in HD and screen for potential disease targets,key protein interactions were mapped and visualized using PPI network analysis.To explore the key pathway of HD intervention in NAFLD.Confirmatory experiment: Forty-eight SD rats were randomly divided into normal group,model group,HD high,medium and low dose groups(200,100 and 50 mg/kg)and silymarin(120 mg/kg)group.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’ 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.H&E staining was used to observe the pathological changes of liver tissues,and Western blot was used to detect the protein expression related to AMPK/ACC signaling pathway.Results: Venn diagram showed that there were 26 potential targets associated with NAFLD disease in HD.The results of PPI protein interaction network diagram and GO enrichment analysis showed that the key pathways of HD intervention in NAFLD disease include linoleic acid metabolism,insulin secretion regulation,lipid oxidation and inflammatory response regulation.Confirmatory experimental 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(P<0.01).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(P<0.05 or P<0.01);ELISA results showed that HD in the middle and high dose groups significantly increased GSH 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(P<0.05 or P<0.01).Western blot showed that HD activated AMPK/ACC signaling pathway and significantly increased pAMPK and p-ACC protein expression in the liver of NAFLD rats(P<0.05 or P<0.01).Conclusion: HD may improve NAFLD by interfering with AMPK/ACC signaling pathway to reduce lipid synthesis,participate in liver anabolism,and counteract oxidative stress and inflammatory response in liver.