基于代谢组学和网络药理学探讨大黄牡丹汤防治结直肠癌的作用机制OA

Objective To investigate the potential mechanism of Dahuang Mudan Decoction(DMD)in the prevention and treatment of colorectal cancer(CRC).Methods Network pharmacology,cellular and ani-mal experiments,and untargeted metabolomics were comprehensively used.Active components of DMD and common targets related to CRC were screened by network pharmacology,followed by enrichment analysis.Human CRC HCT-116 cells were used as the research object.Cell proliferation was detected by CCK-8 and MTT assays,and key proteins in the cGAS-STING pathway were measured by Western Blot.A nude mouse xenograft model of HCT-116 cells was established to evaluate the antitumor effect of DMD in vivo.Serum metabolomics was analyzed by liquid chromatography-mass spectrometry(LC-MS).Results A total of 42 common targets were screened by network pharmacology,with core targets including TP53,IL-6,and AKT1.Enrichment analysis showed that its effects were closely associated with inflammation,immunity,and cancer-related pathways.In vitro experiments revealed that DMD inhibited the proliferation of HCT-116 cells in a concentration-dependent manner and downregulated the expression of cGAS protein.In vivo experiments demonstrated that DMD significantly suppressed xenograft tumor growth(P<0.01)without obvious toxicity.Metabolomics analysis showed that DMD remodeled the serum metabolic profile of tumor-bearing mice,and differential metabolites were mainly enriched in pathways such as lipid metabolism and amino acid metabo-lism.Conclusion DMD may exert anti-colorectal cancer effects synergistically through multiple targets and pathways with favorable safety,providing a theoretical basis for its clinical application.