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Front Pharmacol. 2019 Feb 12;10:94. doi: 10.3389/fphar.2019.00094. eCollection 2019.

Astragalin Suppresses Inflammatory Responses and Bone Destruction in Mice With Collagen-Induced Arthritis and in Human Fibroblast-Like Synoviocytes.

Jia Q1,2,3, Wang T1, Wang X1, Xu H1,2,3, Liu Y1,2,3, Wang Y1,2,3,4, Shi Q1,2,3, Liang Q1,2,3.

Author information

1
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
2
Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
3
Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
4
School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Astragalin, as a bioactive flavonoid with anti-inflammatory, antioxidant, and protective properties, provides a potential agent for rheumatoid arthritis (RA). In this study, its therapeutic efficacy and the underlying mechanisms were explored using DBA/1J mice with collagen-induced arthritis (CIA). It was demonstrated that astragalin could significantly attenuate inflammation of CIA mice. The effects were associated with decreased severity of arthritis (based on the arthritis index), joint swelling and reduced bone erosion and destruction. Furthermore, astragalin treatment suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), and inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) in chondrocytes and synovial cells of CIA mice. Fibroblast-like synoviocytes derived from RA patients (MH7A cells) were applied to verify these effects. In vitro, astragalin inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) dose-dependently in TNF-α-induced MH7A cells, with no apparent cytotoxicity. Furthermore, astragalin suppressed the phosphorylation of p38, JNK, and the activation of c-Jun/AP-1 in TNF-α-induced MH7A cells. In conclusion, it has proven that astragalin could attenuate synovial inflammation and joint destruction in RA at least partially by restraining the phosphorylation of MAPKs and the activating of c-Jun/AP-1. Therefore, astragalin can be a potential therapeutic agent for RA.

KEYWORDS:

CIA; astragalin; fibroblast-like synoviocytes; matrix metalloproteinase; rheumatoid arthritis

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