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Am J Transl Res. 2015 Aug 15;7(8):1371-81. eCollection 2015.

Mangiferin suppresses CIA by suppressing the expression of TNF-α, IL-6, IL-1β, and RANKL through inhibiting the activation of NF-κB and ERK1/2.

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Division of Pharmacotherapy, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
Department of Food Science and Nutrition, Kinki University School of Agriculture Nara, Japan.
Department of Surgery, Kinki University School of Medicine Osakasayama, Osaka, Japan.
Division of Pharmaceutical Organic Chemistry, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
Department of Pathology, Kinki University School of Medicine Osakasayama, Osaka, Japan.


Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of synovial joints, ultimately leading to a progressive and irreversible joint destruction. Activation of nuclear factor-kappa B (NF-κB) promotes production of proinflammatory cytokines in various inflammatory diseases including rheumatoid arthritis. Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside (C-glucosyl xanthone), is a naturally occurring polyphenol. Our previous results showed that mangiferin suppressed NF-κB activation. However, it is unclear, whether mangiferin can prevent rheumatoid arthritis through suppression of NF-κB activation and expression of various cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), which play a critical role in the pathogenesis of rheumatoid arthritis. In the present study, we found that mangiferin suppressed the progression and incidence of CIA in DBA1/J mice. In CIA mice, mangiferin inhibited the mRNA expression of cytokine genes in thymus and spleen of CIA mie and led to decreased serum levels of IL-1β, IL-6, TNF-α, and receptor activator NF-κB ligand (RANKL) via inhibition of NF-κB and activation of extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, mangiferin markedly inhibited not only developing but also clinically evident CIA. These findings suggest that mangiferin has potential clinical applications for the treatment of rheumatoid arthritis.


CIA; ERK1/2; Mangiferin; NF-κB; rheumatoid arthritis


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