Identification of Tumor Necrosis Factor-Alpha (Tnf-α) Inhibitor in Rheumatoid Arthritis Using Network Pharmacology and Molecular Docking
Abstract Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (White peony, WP) in treating rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitor (TNFi) by using network pharmacology and molecular docking. Methods: In this study, the ingredient of WP and the potential targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard and OMIM databases, respectively. Establishment of RA-WP potential target genes interaction network using STRING database. Network maps of WP-RA-potential target genes network was constructed using Cytoscape software. gene ontology (GO), and biological pathway (KEGG) pathway enrichment analysis were used to further explore the RA mechanism and therapeutic effects of WP. Using molecular docking technology to analyze the optimal effective components from WP to docking with TNF-α. Results: 13 active ingredients and 71 target genes were screened from WP, 49 of which intersect with RA target genes and are considered as potential therapeutic targets.Network pharmacological analysis showed that the WP active ingredients of mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, CHRM2. The signaling pathways of the active ingredients for the treatment of RA are TNF-α signaling pathway, toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated-protein kinase, etc. Molecular docking results suggest that mairin was the most appropriate natural TNFi.Conclusions: Our findings provide the essential role and basis, for further studies into the molecular mechanisms of WP and TNFi development in RA.