基于网络药理学、分子对接和动物实验探讨锦红片治疗外科炎性急腹症的作用机制OA

Objective To analyze the the mechanism of action of Jinhong tablets in treating surgical inflammatory acute abdomen by network-pharmacology methods,molecular docking techniques and animal experiments verification.Methods The chemical constituents of Jinhong tablets were retrieved and active components were screened through traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),traditional Chinese medicine and chemical compo-sition database in Shanghai institute of organic chemistry,and TCMbank database,etc;the disease targets were retrieved by searching the Genecards database with the keyword"acute abdomen".Venn diagram was constructed to identify potential tar-gets for the treatment of surgical inflammatory acute abdomen with Jinhong tablets;and Cytoscape 3.8.2 software was used to construct a PPI network and Mcode module clustering for screening key targets in the active ingredients-action targets-inflam-matory acute abdomen disease of Jinhong tablets.Cb-Dock2 online tools and Pymol software were used to perform molecular docking and visualization display of effective ingredients such as kaempferol and puerarin with the target to be validated.Then,LPS was used to induce acute biliary tract infection in rats for validation.Results The network pharmacology meth-odology established for Jinhong tablets revealed a TCM-component-target-pathway network comprised 13 active components(including kaempferol,aloe-emodin,etc.),corresponding to 25 potential targets(PTGS2,AKT1,etc.)and 10 KEGG pathways(cancer pathway,TNF signaling pathway,MAPK signaling pathway,proteoglycans in cancer,etc.).Molecular docking results demonstrated strong binding affinity between 6 bioactive components(including kaempferol,euparin and aloe-emodin)had good binding affinity with targets such as AKT1 and inducible nitric oxide synthase(NOS2),and the visu-alization process displayed 8 binding states.Animal studies indicated that Jinhong tablets could reduce AKT1 and NOS2 expression in bile duct tissues of LPS-induced acute cholangitis rats,decrease serum malondialdehyde(MDA)levels,ele-vate serum glutathione(GSH)concentrations,and enhance superoxide dismutase(SOD)activity.Conclusion This study demonstrates from multiple dimensions such as network-pharmacology,molecular docking,and animal experiments that the traditional Chinese medicine compound Jinhong tablets,in a"multi-component,multi-target,and multi-pathway"manner,regulate AKT1 and NOS2 through effective components such as kaempferol,puerarin,and aloe-emodin in a"multi-compo-nent,multi-target,and multi pathway"manner,thereby affecting serum levels of SOD,GSH,and MDA,and exerting a therapeutic effect on surgical inflammatory acute abdomen.