Molecular mechanism of Si-Miao-Yong-An decoction in the treatment of diabetic foot microcirculation and network pharmacology information analysis results

Abstract

OBJECTIVE: This study aims to explore the effect and mechanism of Si-Miao-Yong-An decoction (SMYAD) on diabetic foot by simulating the microenvironment of diabetic foot in vitro, and further verify these results using bioinformatics analysis technology, in order to provide a basis for the treatment of diabetic foot with traditional Chinese medicine. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxia to simulate the microcirculation of diabetic foot. Then, these were administered with SMYAD for intervention. Afterward, the cell viability was detected by MTT assay, the apoptosis was detected by flow cytometry, and the STAT3 signaling pathway and Bcl-2 and Bax protein expression were detected by Western blot. Next, TCMSP was used to determine the chemical composition and target gene information of the SMYAD, and the GeneCards database was used to search for the disease-related target gene information of diabetic foot. Furthermore, the Venny 2.1 online software was used to screen and obtain the drug–disease common target genes for the SMYAD and diabetic foot. The common target genes were entered into the STRING database for retrieval, in order to construct the network diagram for protein-related action, and the R software was used to analyze the pathway enrichment, in order to explore the mechanism of the SMYAD in the treatment of diabetic foot microcirculation. RESULTS: Compared with the control group, the SMYAD increased the activity of HUVECs cultured in the hypoxia state but decreased the apoptosis rate. Furthermore, the protein expression of p-STAT3 and Bcl-2 increased, and the protein expression of Bax decreased (P < 0.05). A total of 235 drug-related target genes were found by screening, and 4553 target genes related to diabetic foot were obtained. The Venny software analysis revealed that there were 171 drug–disease interaction target genes. The STRING database and the GO and KEGG functional enrichment analysis revealed that STAT3, AKT, MAPK, and other proteins were involved, and that these may be correlated to the mechanism of the SMYAD in the treatment of diabetic foot microcirculation. CONCLUSION: SMYAD can affect the expression of Bcl-2 and Bax genes by regulating the activity of the STAT3 signaling pathway, playing a role in the treatment of diabetic foot.