Integrative Network Pharmacology Analysis of Tripterygium Wilfordii Against Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent synovial inflammation, progressive cartilage destruction, bone erosion and joint deformity, leading to severe disability and reduced quality of life. Tripterygium wilfordii Hook. F. (Thunder God Vine), a well-known medicinal plant in traditional Chinese medicine has been extensively used for the treatment of autoimmune and inflammatory disorders due to its potent immunosuppressive and anti-inflammatory properties. Although conventional therapies are effective, they are often associated with adverse effects and incomplete disease remission, highlighting the need for safer and effective therapeutic strategies. This study aimed to explore the molecular mechanisms underlying the therapeutic effects of Tripterygium wilfordii against RA using a network pharmacology approach. Active phytoconstituents including triptolide, celastrol, and wilforlide A, were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and PubChem. Potential molecular targets were predicted using Swiss Target Prediction, while RA-associated genes were retrieved from the GeneCards and DisGeNET databases. Overlapping targets were identified through Venn analysis, followed by Protein–Protein Interaction (PPI) network construction using the STRING database. Hub genes were screened using the CytoHubba plugin in Cytoscape, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the biological functions and signaling pathways involved. The analysis identified TNF, IL6, AKT1, MAPK1, and NF-κB as major hub targets involved in inflammatory and immune responses. KEGG pathway enrichment analysis highlighted the PI3K–Akt, MAPK, TNF, and NF-κB signaling pathways as key mechanisms mediating the therapeutic effects. These findings suggest that Tripterygium wilfordii exerts anti-rheumatic activity through a multi-component, multi-target, and multi-pathway mode of action, providing valuable insights into its pharmacological basis and supporting its potential as a promising therapeutic candidate for rheumatoid arthritis.