The integration of network pharmacology and multi-omics reveals the mechanism of the leaves of Malus hupehensis in inhibiting acute liver injury
Objective The leaves of Malus hupehensis (MH) are a medicinal and edible TCM with good liver protection, but the mechanism of hepatoprotective effect of MH is not clear. In this study, the network pharmacology integrated multi-omics method was used to explore the hepatoprotective mechanism of MH.Methods Transcriptomics and metabolomics were used to further explore the mechanism of MH at the gene and metabolite levels, and the effect was verified by immunohistochemistry, Western blot analysis and RT-qPCR.Results Our analysis identified 121 in vitro and 20 in vivo components of MH. Network pharmacology analysis showed that phlorizin and phloretin, the prototype components of MH, were involved in inflammation and metabolism-related pathways. In vivo experiments showed that MH effectively inhibited carbon tetrachloride-induced ALI in mice through antioxidant and anti-inflammatory effects. The combined analysis of network pharmacology and multi-omics showed that MH exerted liver protection by inhibiting the activation of MAPK signaling pathway and regulating metabolic reprogramming (lipid metabolism, amino acid metabolism).Conclusion MH exerts a protective effect on ALI by inhibiting MAPK signaling pathway and regulating lipid and amino acid metabolism reprogramming. This study provides new insights into the development of drugs for the prevention and treatment of ALI based on MH.