Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Scutellaria barbata plus Hedyotis diffusa herb pair on esophageal squamous cell carcinoma

Abstract

Objective: This study aims to systematically investigate the therapeutic targets and molecular mechanisms of Scutellaria barbata plus Hedyotis diffusa herb pair (SBHD) on esophageal squamous cell carcinoma (ESCC)based on GEO gene microarray combined with network pharmacology and molecular docking technology. Methods: The active components and effective targets of SBHD were retrieved and downloaded from the TCMSP database, and the differentially expressed genes (DEGs) of ESCC were retrieved and downloaded from the GEO database. The intersection targets between medicine target genes and disease target genes were screened by drawing Venn diagram. Bioinformatics tools such as R language, Cytoscape software, STRING platform, and DAVID platform, were applied to perform active components-targets regulatory network analysis, PPI network analysis, and GO and KEGG pathway enrichment analysis. Molecular docking was performed to validate the interaction between the core active components and the key target genes by AutoDock Vina tools. Results: A total of 33 main active componentswere predicted from herb pair, and 28 intersection targets were screened from 105 medicine target genes and 4064 disease target genes. A topological analysis of the active components-targets regulatory network and PPI network revealed 5 core ingredients and 6 key targets for SBHD treating ESCC, respectively. KEGG enrichment analysis found that SBHD could affect cellular senescence, hepatitis B, MAPK signaling pathway, proteoglycans in cancer and apoptosis in ESCC. Molecular docking found that the 5 core active compounds had good binding properties with the 6 key therapeutic targets. Conclusion: The therapeutic effects of SBHD on ESCC might be related to the active components including quercetin, baicalein, luteolin, stigmasterol and wogonin, which intervened with the key targets including IL6, CASP3, MYC, AR, CAV1 and RUNX2, and the signaling pathway including cellular senescence, hepatitis B, MAPK signaling pathway, proteoglycans in cancer and apoptosis.