[Integrating network pharmacology and metabolomics to explore mechanism of Tricholoma matsutake extracts on alcoholic liver injury in mice].

A metabolomics study was conducted on serum and liver samples from mice with alcoholic liver injury induced by the National Institute on Alcohol Abuse and Alcoholism(NIAAA). This was combined with network pharmacology to investigate the ameliorative effect of Tricholoma matsutake extracts on alcoholic liver injury in mice and its underlying mechanism. Serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), and triglyceride(TG) were measured, while liver pathological changes were assessed by hematoxylin-eosin(HE) staining. Moreover, differential metabolites in serum and liver were detected by gas chromatography-mass spectrometry(GC-MS), and potential targets of T. matsutake extracts were analyzed via network pharmacology. The predicted targets were compared with those associated with differential metabolites to explore key targets involved in the amelioration of alcoholic liver injury by the extract. The results showed that, compared with the pathological model group, the T. matsutake extracts treatment group showed significantly reduced serum ALT, AST, and TG levels, along with improved lipid vacuolation and hepatocyte morphology, indicating a significant ameliorative effect of the extract on alcoholic liver injury in mice. The metabolomics results revealed that the extract modulated 12 differential metabolites in liver tissues, including glucose, glutamate, leucine, and phenylalanine, and 31 differential metabolites in serum, including alanine, cholesterol, glucose, lactose, and methionine. Further network pharmacology analysis suggested that T. matsutake extracts may ameliorate alcoholic liver injury primarily by targeting pathways related to Myc and Cat, influencing genes such as Aldh9a1, Aldh3a2, Aldh2, Hsd17b4, Ehhadh, Acox1, Acaa1, Acot1, and Gls. These were mainly involved in five metabolic pathways: cysteine and methionine metabolism, arginine biosynthesis, and alanine, aspartate, and glutamate metabolism. In conclusion, T. matsutake extracts may ameliorate alcoholic liver injury in mice by regulating amino acid metabolism and glucose metabolism through pathways associated with Myc and Cat.