The Ethyl Acetate Fraction of Microsorum fortunei (T. Moore) Ching Alleviates Rheumatoid Arthritis via Multi‐Target Mechanisms: An Integrated Strategy Combining UPLC‐Q‐TOF/MS, Network Pharmacology, and Experimental Validation

Microsorum fortunei (T. Moore) Ching (MF) is a traditional Chinese medicine utilized for the treatment of rheumatoid arthritis (RA). However, the chemical composition and underlying mechanisms of MF remain unclear. This study aims to identify the active ingredients of MF that contribute to its therapeutic effects on RA and to explore the associated mechanisms. A rat model of RA was established, and the effects of MF were evaluated by monitoring changes in appearance, body weight, inflammatory indices, joint histopathology, thymus and spleen indices, and levels of inflammatory factors. The ethyl acetate fraction of MF (EAF-MF) was analyzed using UPLC-Q-TOF/MS. Network pharmacology and molecular docking analyses were conducted to predict the anti-inflammatory components and pathways. The EAF-MF significantly alleviated RA symptoms, leading to reductions in foot swelling, arthritis index, joint damage and pro-inflammatory cytokines. UPLC-Q-TOF/MS identified 57 compounds within the EAF-MF; network pharmacology identified 44 active components connecting 524 targets. The data showed that MF treatment of RA was related to oxytocin signaling pathway and Cushing syndrome. Molecular docking confirmed strong binding between core targets and key components. Consequently, this study elucidates the multi-component, multi-target, and multi-pathway mechanisms of EAF-MF in the treatment of RA, thereby supporting its clinical application.