Abstract:Abstract: [Purposes]To investigate the therapeutic effects of Cynanchum paniculatum root extract on rheumatoid arthritis (RA) and to reveal the underlying molecular mechanisms. [Methods]A rat model of antigen-induced rheumatoid arthritis (AIA) was constructed using complete freund''s adjuvant (CFA), and different concentrations of C. paniculatum root extract were administered orally. Subsequently, paw swelling, body weight, and organ index of rats were measured, and ELISA was used to detect serum pro-inflammatory factor levels, myeloperoxidase (MPO) content in ankle tissues, and RT-qPCR to detect the mRNA expression levels of key genes of the NF-κB pathway.In addition, GC-MS was used to analyze and identify the components of the C. paniculatu root extract. [Findings] Compared with the model group, the experimental group of C. paniculatu root extract effectively eliminated paw swelling in rats.And serum levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) as well as MPO content in ankle tissues were significantly reduced (p<0.001) in a dose-dependent manner. In addition, the body weight and the growth and development of immune organs of rats were not affected by the extract of C. paniculatum root. Meanwhile, RT-qPCR results showed that the mRNA expression levels of NF-κB, TNF-α, IL-6, and interleukin 1β (IL-1β) genes were significantly (p<0.001) decreased by the methotrexate group and the experimental group with 500 mg?kg-1 and 250 mg?kg-1 of C. paniculatum root extract compared with the model group in a dose-dependent manner..GC-MS results showed that the root extract of C. paniculatu mainly contained paeonol, palmitic acid, linoleic acid, and 5-hydroxymethylfurfural.[Conclusions]C. paniculatum root extract showed good RA therapeutic effects, which may act primarily through paeonol and linoleic acid, and the preliminary reveals that its therapeutic mechanism may be related to the regulation of NF-κB pathway.