Kadsua coccinea Extract Alleviates Rheumatoid Arthritis via TNF-α Suppression and Gut Microbiota Modulation

Hao Zheng,1,2,* Jiaxin Yang,1,* Yasi Deng,1 Bowen Zhang,1 Fan Bai,1 Yuxin Chen,1 Yunmi Lu,1 Beier Lian,1 Juan Huang,1 Yupei Yang,1 Wei Wang,1 Huanghe Yu1 1TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 2Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmacy, Changsha Medical University, Changsha, 410219, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huanghe Yu, TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email [email protected] Wei Wang, TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email [email protected] and Purpose: Kadsura coccinea, Lem. A. C. Smith (KCR) is a traditional multi-ethnic medicinal plant in China, widely used by Yao, Dong, and other ethnic groups in Hunan, Yunnan, Guangxi, and other southern regions. Traditionally prepared as medicinal wine, it has shown notable therapeutic advantages in treating rheumatoid arthritis (RA), though its underlying mechanism remains unclear.Methods: This study evaluated the anti-RA effects of KCR ethanol extract in vitro and in vivo using LPS-induced RA fibroblast-like synoviocytes (RAFLS) and inflammatory macrophages (RAW264.7), as well as an adjuvant-induced arthritis (AIA) rat model generated with inactivated Mycobacterium tuberculosis. Mechanisms were explored via network pharmacology, molecular biology, and gut microbiota analysis.Results: KCR extract suppressed TNF-α, IL-1β, and IL-6 expression in LPS-stimulated RAFLS and RAW264.7 cells. It markedly inhibited paw swelling, synovial hyperplasia, and bone destruction in AIA rats, potentially by downregulating TNF-α, IL-1β, and IL-6 in paw tissues and modulating gut microbiota (Corynebacterium and Jeotgalicoccus). At 3000 mg/kg, no significant histopathological or hematological toxicity was observed.Conclusion: Collectively, KCR alleviates joint pathologies in AIA rats by suppressing TNF-α-driven inflammation and modulating gut microbiota, with Corynebacterium and Jeotgalicoccus identified as potential mediators of the TNF-α-gut axis. These findings underscore KCR’s anti-RA efficacy and mechanisms, providing a theoretical basis for its safe clinical application and promoting further development. Keywords: Yao ethnomedicine, Kadsura coccinea (Lem.) A. C. Smith, rheumatoid arthritis, inflammatory response, gut microbiota