Active Components and Multi-target Mechanism of Tibetan Sinopodophyllum hexandrum Medicine Against Rheumatoid Arthritis Using a CFA-induced Arthritis Rat Model

<i>Sinopodophyllum hexandrum</i> ("Taoerqi") is a traditional Tibetan medicine used for treating inflammation and arthralgia, but its therapeutic basis against rheumatoid arthritis (RA) remains unclear. This study aimed to identify its active anti-RA fraction, analyse its chemical composition, and explore its mechanisms of action. Using a CFA-induced arthritis rat model, the dichloromethane fraction of <i>S. hexandrum</i> (SHD) was evaluated for anti-RA activity. UHPLC-Q-TOF-MS/MS identified 57 compounds, mainly prenylated flavonoids and arylnaphthalene lignans. Network pharmacology predicted their targets, and <i>in vitro</i> assays on TNF-<i>α</i>-induced fibroblast-like synoviocytes confirmed the anti-RA effects of 15 isolates. Enzyme inhibition, molecular docking, surface plasmon resonance, and Western blot validated their interactions with TNF-<i>α</i> and JAK1. Oral administration of SHD significantly reduced paw swelling and neutrophil infiltration in RA rats. These findings suggest that prenylated flavonoids and arylnaphthalene lignans are key active components exerting anti-RA effects, respectively, via TNF-<i>α</i> and JAK1 inhibition, highlighting their potential for further drug development.