Network pharmacology integrated with molecular docking and molecular dynamics simulations to explore the mechanism of Shaoyao Gancao Tang in the treatment of asthma and irritable bowel syndrome.

Abstract

Background: Numerous studies have demonstrated a correlation between asthma and irritable bowel syndrome (IBS). The Chinese herbal compound Shaoyao Gancao Tang (SYGCT) has been found to have therapeutic effects on both asthma and IBS, but the underlying mechanisms are not yet fully understood. This study aims to explore the key components, key targets, and potential mechanisms of SYGCT in treating asthma with IBS by using network pharmacology, molecular docking techniques and molecular dynamics simulation.

Methods: The major chemical components and potential target genes of SYGCT were screened by bioinformatics. The key targets of Asthma-IBS comorbidity were identified based on network modules. The intersection of the drug targets and disease targets was identified as the potential targets of SYGCT in treating asthma-IBS. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to identify the biological processes and signaling pathways involved in these potential targets. A protein-protein interaction network was constructed to identify hub targets, while a drug-compound-target topological network was built to screen key compounds. Molecular docking was used to verify the affinity between the hub targets and key compounds. Molecular dynamics analysis was utilized to assess the binding stability of these interactions.

Results: Network pharmacology analysis revealed that the therapeutic effect of SYGCT on asthma-IBS involved multiple biological processes and signaling pathways. It may exert therapeutic effects primarily through signaling pathways such as IL-17, TNF, and Th17 cell differentiation. The possible targets of SYGCT in the treatment of asthma-IBS could be IL6, TNF, JUN, PTGS2, STAT3, IL1B, CASP3, NFKBIA, IL10, and PPARG. Molecular docking verification showed that the predicted targets had good binding affinity with the compounds, among which PTGS2, CASP3, and PPARG had higher binding energy. Molecular dynamics simulation revealed that PTGS2, CASP3, and PPARG proteins had good stability and high binding strength with the compounds 2-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[6,5-f]chromen-3-yl]-5-methoxyphenol and shinpterocarpin.

Conclusion: SYGCT plays a therapeutic role in asthma and IBS through multiple targets and pathways, providing a theoretical basis for explaining the mechanism and clinical application of SYGCT in treating different diseases with the same treatment in asthma and IBS.