國家衛生研究院 NHRI:Item 3990099045/11084
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    題名: Chondroprotective effects and mechanisms of dextromethorphan: Repurposing antitussive medication for osteoarthritis treatment
    作者: Chen, LW;Liu, FC;Hung, LF;Huang, CY;Lien, SB;Lin, LC;Lai, JH;Ho, LJ
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study. Chondrocytes were prepared from cartilage specimens taken from pigs or OA patients. Western blotting, quantitative PCR, and immunohistochemistry were adopted to measure the expression of collagen II (Col II) and matrix metalloproteinases (MMP). DXM significantly restored tumor necrosis factor-alpha (TNF-alpha)-mediated reduction of collagen II and decreased TNF-alpha-induced MMP-13 production. To inhibit the synthesis of MMP-13, DXM blocked TNF-alpha downstream signaling, including I kappa B kinase (IKK)alpha/beta-IkappaBalpha-nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK)-activator protein-1 (AP-1) activation. Besides this, DXM protected the CIA mice from severe inflammation and cartilage destruction. DXM seemed to protect cartilage from inflammation-mediated matrix degradation, which is an irreversible status in the disease progression of osteoarthritis. The results suggested that testing DXM as an osteoarthritis therapeutic should be a focus in further research.
    日期: 2018-03-12
    關聯: International Journal of Molecular Sciences. 2018 Mar 12;19(3):Article number 825.
    Link to: http://dx.doi.org/10.3390/ijms19030825
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000428309800182
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85044159172
    顯示於類別:[何令君] 期刊論文

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