Effect of Xiaoyao Wan on endogenous metabolites in feces of rats with metabolic associated steatohepatitis
Objective To explore the effect and its mechanism of Xiaoyao Wan on metabolic associated steatohepatitis in rats using metabolomics technology.Methods Twenty-four SD male rats were randomly divided into three groups:control group,model group and Xiaoyao Wan group(XYW group).The rats in model group and XYW group were given high-fat diet,subcutaneous injection of CCl4,hunger and satiety disorder,and tail clamping stimulation to establish the model of metabolic associated steatohepatitis for four weeks.After successful modeling,the rats in XYW group were given Xiaoyao Wan water solution[0.334 8g/(kg· d)]for four weeks.During this period,the general status of rats was observed.Serum biochemical indexes,T-CHO,TG,ALT,AST,LDL-C,MCP-1,TNF-α,IL-6,IL-10,and oxidative stress indicators MDA and SOD were detected in rats after administration in different groups.Patho-logical changes of liver tissues were stained with HE.Faecal metabolites in rats were analyzed using 1H-NMR.Results Rats in model group had darker hair,and were more likely to be irritated,depressed and listless,with slow movements,poorer appetite and looser defecation.The general status of rats in XYW group was significantly improved compared with model group.Compared with control group,the serum levels of T-CHO,TG,ALT,AST,LDL-C,MCP-1,TNF-α and IL-6 in model group were significantly increased(all P<0.05),while the level of IL-10 was significantly decreased(P<0.05).Compared with model group,the levels of T-CHO,TG,ALT,AST,LDL-C,MCP-1,TNF-α and IL-6 were significantly decreased(all P<0.05),while the level of IL-10 was significantly increased in XYW group(P<0.05).Compared with control group,the MDA level was significantly increased in model group(P<0.01),while the SOD level was significantly decreased(P<0.01).Compared with model group,the MDA level was significantly decreased in XYW group(P<0.01),while SOD level was significantly increased(P<0.01).HE staining results showed an increase in hepatic fat vacuoles and inflammatory cell infiltration in model group compared with control group.Compared with model group,liver fat vacuoles and inflammatory cell infiltration were decreased in XYW group.Metabonomics results showed significant changes in the levels of hypoxanthine,D-glucose,N-acetylglycoprotein,propionic acid,leucine,tyrosine,choline,formic acid,D-xylose and threonine metabolites in the faeces in model group compared with control group(all P<0.05),including the biosynthesis of phenylalanine,tyrosine and tryptophan,and the metabolism of tyrosine in various metabolic pathways.Compared with model group,the levels of hypoxanthine,D-glucose,N-acetylglycoprotein,propionic acid,leucine,tyrosine,choline,formic acid,D-xylose and threonine metabolites in the faeces in XYW group showed a significant regression(all P<0.05).Conclusion Xiaoyao Wan can protect hepatocytes by improving amino acid metabolism and lipid metabolism,and reducing glucose metabolism disorder,oxidative stress and inflammatory damage,thus improving the metabolic associated steatohepatitis.
Xiaoyao Wanmetabolic associated steatohepatitis(MASH)1 H nuclear magnetic resonance(1 H-NMR)fecalmetabolomics