Suppression of inflammatory responses after onset of collagen-induced arthritis in mice by oral administration of the Citrus flavanone naringin

Abstract

Rheumatoid arthritis (RA) is closely related to the pathogenesis of tumor necrosis factor α in lesions. We investigated the suppressive effects of a Citrus flavanone naringin on inflammatory responses in mice with collagen-induced arthritis (CIA), a mouse model for RA. To investigate potential preventive and therapeutic effects of naringin, mice were given naringin orally three times a week from the second immunization with collagen (day 21) and from day 31, when symptoms of CIA had reached a plateau, respectively. In both cases, inflammation-related clinical scores for knee joints were significantly reduced by administration of naringin. Histological analyses demonstrated that representative phenomena, such as damage to interchondral joints, infiltration of inflammatory cells and pannus formation, were significantly depressed by treatment with naringin. In addition, increases in the expression of high-mobility group box-1 protein in the joints of mice with CIA were suppressed by naringin. These results suggest that oral administration of naringin might be effective for treating human patients with RA.

Keywords::

• Collagen-induced arthritis
• inflammation
• TNF-α
• rheumatoid arthritis
• flavonoid
• naringin

Acknowledgments

The authors thank Ryo Miyake, Yoshihide Hibi, Hirotoshi Aono, Kana Shindo, Yukari Ono, Yuya Kawai and Kenro Takase for their technical assistance. We would like to thank Dr. Tsukasa Matsumoto for his helpful discussion.

Declaration of interest

This study was supported, in part, by a Grant-in-Aid for Scientific Research Collaboration from Kitasato University (to Y.K.).