Network pharmacology and molecular docking to explore the treatment potential and molecular mechanism of Si-Miao decoction against gouty arthritis

Abstract

Gouty arthritis (GA) is a common metabolic rheumatological disease. Si-Miao decoction has therapeutic effects on GA. In our study, we investigated the mechanism of Si-Miao decoction against GA using network pharmacology and molecular docking analytical methods. The Traditional Chinese Medicine Systems Pharmacology Database was used as the basis for screening the main targets and agents of the Si-Miao decoction, and the Genecards, OMIM, and Drugbank databases were used to screen GA-related targets. They were analyzed using Venn with the drug targets to obtain the intersection targets. We used Cytoscape 3.9.1 to draw the “Drugs-Compounds-Targets” network and the String database for creative protein-protein interaction networks of target genes and filtered core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze the core targets. Molecular docking was performed using AutoDockTools to predict the binding capacity between nuclear targets and active components in the Si-Miao decoction. A total of 50 chemically active components containing 53 common targets of Si-Miao decoction anti-GA and 53 potential drug target proteins were identified. Core targets, namely, TNF, STAT3, SRC, PPARG, TLR4, PTGS2, MMP9, RELA, TGFB1, and SIRT1, were obtained through PPI network analysis. GO and KEGG analyses showed that the mechanism of anti-GA in Si-Miao decoction may proceed by regulating biological processes such as inflammatory factor levels, cell proliferation, apoptosis, and lipid and glucose metabolism, and modulating the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, NF-kappa B signaling pathway, and Toll-like receptor signaling pathway. We further screened the core targets, including PTGS2, MMP9, and PPAGR, as receptor proteins based on their degree value and molecular docking with the main active compounds in Si-Miao decoction, and found that baicalein had high affinity. In conclusion, Si-Miao decoction, through anti-inflammatory, apoptosis-regulating, and anti-oxidative stress action mechanisms in the treatment of GA.