Cinnamomi Ramulus (CR) has been extensively used as a remedy for inflammatory diseases in China. This study adopted an integrative approach of experimental research, phytochemistry, and network pharmacology to investigate its alleviative effects on rheumatoid arthritis (RA) and the underlying potential mechanisms. CR extract (50, 100, and 200 mg/kg) and methotrexate (MTX) significantly ameliorated RA symptoms in the collagen-induced arthritis (CIA) rat model. They also reduced paw volume, arthritis index, proinflammatory cytokines (TNF-α, IL-17A, IL-6, and IL-1β), and oxidative damage. Sixty-three compounds were systematically identified as the basic components of CR. Fifty-five common genes obtained from compounds and GEO databases were employed to construct the protein-protein interaction (PPI) network. Among them, 20 hub genes were identified via the cytoHubba. Enrichment analysis of the common genes indicated that the TNF signaling pathway and IL-17 signaling pathway might be the potential key pathways. Moreover, molecular docking methods confirmed the high affinity between the top 10 bioactive components of CR and the top 10 targets. In addition, in vitro results showed that CR extract (0.2, 0.4, and 0.8 mg/mL) inhibited inflammation and oxidative damage in MH7A cells stimulated by lipopolysaccharide (LPS). In summary, this study adopted multiple approaches to elucidate the protective effect and potential mechanisms of CR on RA, indicating that CR might be a promising herbal candidate for further investigation of RA treatment.
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