title: 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.
abstract: 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.
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Tsubaki
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kino
authors.affiliation: Department of Food Science and Nutrition, Kinki University School of Agriculture Nara, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Surgery, Kinki University School of Medicine Osakasayama, Osaka, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Imano
authors.affiliation: Division of Pharmaceutical Organic Chemistry, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
authors.forename: Genzo
authors.initials: G
authors.lastname: Tanabe
authors.affiliation: Division of Pharmaceutical Organic Chemistry, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
authors.affiliation: Department of Pathology, Kinki University School of Medicine Osakasayama, Osaka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Satou
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy Kowakae, Higashi-Osaka, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Nishida
keywords: CIA; ERK1/2; Mangiferin; NF-κB; rheumatoid arthritis