Circaea mollis Sieb. & Zucc., a genus of Circaea that follows Onagraceae, has been used for centuries as a folk herb in traditional Chinese medicine (TCM) and Hani Ethnopharmacy for the treatment of joint swelling and pain in rheumatoid arthritis.This study was designed to confirm anti-arthritic effects and its underlying mechanism of ethanol extracts of Circaea mollis Sieb. & Zucc. (EEC), which may contribute to provide the pharmacological basis in the treatment of rheumatoid disease.Dimethylbenzene (DMB)-induced inflammatory swelling model, hot-plate pain model in mice and Freund's complete adjuvant (FCA)-induced arthritis model in rats were used to evaluate the anti-arthritis effect of EEC. Arthritis severity was done by measuring inflammatory swelling, pain threshol, paw swelling, arthritis index, body weight, spleen index and thymus index. The levels of TNF-α, IL-1β and IL-10 in sera were measured using ELISA. The pathological change of the ankle joint was also done. Phenolic composition of EEC was analyzed.EEC inhibited inflammatory swelling and increased heat-induced pain threshold in mice. Furthermore, EEC significantly alleviated paw swelling and arthritis index, decreasing the spleen index and thymus index. Besides, EEC down-regulated the serum TNF-α and IL-1β, and increased the production of serum IL-10 in FCA-induced rats. Histopathological examination demonstrated that EEC can effectively relieve synovial hyperplasia, control the infiltration of the inflammatory and protect cartilage from destruction.Our work demonstrated that EEC possessed the potential therapeutic effect against arthritis in rodents which was attributed to modulating proinflammatory cytokines TNF-α, IL-1β and anti-inflammatory factors IL-10. Flavonoids and polyphenols may contribute to the therapeutic effect of EEC on arthritis.
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