| Objective: To analyze the effective components,targets and mechanism of Sanmiao Jiedu Liquid in treating diabetic foot ulcer(DFU)by using network pharmacology technology,and to observe the clinical efficacy of Sanmiao Jiedu Liquid in treating DFU with damp-heat excess by waterlogging.Methods: In study one,Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TSMSP)was used to screen the effective components and targets genes of Sanmiao Jiedu Liquid;the disease-related targets genes of DFU were jointly mined by combining multiple databases,and the common targets genes of Sanmiao Jiedu Liquid-DFU were obtained.On the basis of constructing the TCM regulatory network and protein-protein interaction(PPI)network,the core components of Sanmiao Jiedu Liquid and its core targets were screened out.The enrichment analysis of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were carried out on the common targets genes to identify the signaling pathways involved in the treatment of DFU with Sanmiao Jiedu Liquid.Finally,molecular simulation software and molecular threedimensional structure display software were used to carry out molecular docking between core components and core targets genes.In study two,65 DFU patients with damp-heat excess who met the criteria were randomly divided into an observation group and a control group.Both groups were given routine basic treatment.On the basis of this,patients in the observation group were treated with local waterlogging of Sanmiao Jiedu Liquid and those in the control group were treated with local waterlogging of Kangfuxin Liquid for a total of 14 days.General data of the two groups(gender,age,duration of ulcer,Wagner classification,ABI,and species of flora)were collected.The TCM syndrome score,wound surface area,and serum TNF-α and IL-6 levels of the two groups before and after treatment were observed and compared.The wound healing rates of patients in the two groups after treatment were calculated.The efficacy and safety indicators of the two groups were evaluated.Results: In study one,325 potential targets of effective components in Sanmiao Jiedu Liquid and 711 DFU targets were obtained.The core components of Sanmiao Jiedu Liquid in treating DFU were quercetin,apigenin,puerarin and daidzein,and the core targets were signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase14(MAPK14),estrogen receptor(ESR1)and histone acetyltransferase p300(EP300).2159 items of biological process,60 items of cell composition and 155 items of molecular function were obtained by GO enrichment analysis.170 signaling pathways were obtained by KEGG analysis.Molecular docking showed that the core components and core targets could be effectively and autonomously combined.In study two,1.The total effective rate of patients in the observation group after treatment was superior to that in the control group(P < 0.05).2.TCM syndrome scores of patients in the two groups after treatment were lower than those before treatment(P <0.05),and the observation group was superior to the control group(P <0.05).The symptom scores of the two groups after treatment were all lower than those before treatment(P < 0.05).The wound pus color score,wound granulation color score and wound granulation particle score of the observation group were better than those of the control group(P < 0.05).3.The wound area of patients in the observation group after treatment was smaller than that before treatment(P < 0.05),and it was better than that in the control group(P < 0.05).4.The levels of serum TNF-α and IL-6 in the two groups after treatment were lower than those before treatment(P< 0.05),and the observation group was superior to the control group(P <0.05).No adverse events were observed in the two groups during the treatment.Conclusion:1.Quercetin,apigenin,puerarin and soybean isoflavone,the core components of Sanmiao Jiedu Liquid,may act on the core targets STAT3,MAPK14,ESR1 and EP300,and then interfere with multiple inflammatory signaling pathways to achieve the effect of treatment of DFU.2.The treatment with waterlogging of Sanmiao Jiedu Liquid can improve the local symptoms of limbs in DFU patients with damp-heat excess,promote wound healing,and reduce serum TNF-α and IL-6 levels. |