Exploring the mechanism of Cynanchum paniculatum (Bunge) Kitag’s therapeutic strategy for rheumatoid arthritis: integrating network pharmacology, molecular docking and in vivo experiments

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by joint swelling, cartilage degradation, and joint deformity. The traditional Chinese herb Cynanchum paniculatum (Bunge) Kitag has been utilized in the management of RA, but the underlying mechanisms are unknown. This study utilized network pharmacology analysis to identify 26 active compounds associated with RA treatment and elucidate their interactions with 23 critical targets linked to RA. Subsequently, molecular docking studies revealed eight compounds with the capacity to bind to multiple key targets, with butyl isobutyl phthalate and geranyl acetone emerging as the most promising candidates based on their drug-likeness properties. To validate these findings, a rat model of adjuvant-induced arthritis was employed. Oral administration of geranyl acetone led to a significant reduction in paw swelling and pro-inflammatory markers, including TNF-α, IL-6, IL-1β, and MPO. Furthermore, it resulted in histological improvements in ankle tissues, all without adverse effects on weight or immune organs. Mechanistically, geranyl acetone was found to impede the progression of RA by modulating the TLR4/MyD88/NF-κB signaling pathway. In conclusion, C. paniculatum demonstrates substantial therapeutic potential for RA due to its multi-target and multi-pathway activities. Moreover, geranyl acetone, when used as a standalone agent, exhibits significant promise in alleviating RA symptoms, offering a compelling avenue for further research and potential clinical applications. 26 active C. paniculatum compounds interact with 23 RA targets Network pharmacology and molecular docking identifies RA candidates Geranyl acetone alleviates RA symptoms without side effects Geranyl acetone mitigates RA via TLR4/MyD88/NF-κB pathway modulation