2. Academic Validation
  3. Zafirlukast attenuates advanced glycation end-products (AGEs)-induced degradation of articular extracellular matrix (ECM)

Zafirlukast attenuates advanced glycation end-products (AGEs)-induced degradation of articular extracellular matrix (ECM)

  • Int Immunopharmacol. 2019 Mar;68:68-73. doi: 10.1016/j.intimp.2018.12.056.
Changjiang Lei 1,  Shixing Wu 2,  Chong Wen 3,  Yuan Li 1,  Ning Liu 1,  Jianbin Huang 1,  Lei Li 1,  Meixia Fu 4,  Jiani Liu 5
Affiliations

Affiliations

  • 1 Department of General Surgery, Fifth Hospital of Wuhan, Wuhan, Hubei 430000, China.
  • 2 Department of Hepatobiliary Surgery, Renmin Hospital Hu Bei University of Medicine, Shiyan, Hubei 430000, China.
  • 3 Department of Traditional Chinese Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, China.
  • 4 Department of Pharmacy, Fifth Hospital of Wuhan, Wuhan, Hubei 430000, China. Electronic address: alan2311@yeah.net.
  • 5 Department of Geriatrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, China. Electronic address: liujn2567@163.com.
PMID: 30612086 DOI: 10.1016/j.intimp.2018.12.056
Abstract

Zafirlukast, a Leukotriene Receptor antagonist, has been shown to exert a wide range of effects including anti-asthmatic, anti-inflammatory and oral anti-bacterial. Osteoarthritis is one of the most prevalent age-related public health burdens in the modern world. In the present study, we applied zafirlukast in the treatment of human primary chondrocytes and found that it exerts potent anti-osteoarthritic effects. Zafirlukast inhibited AGEs-induced degradation of the articular extracellular matrix by suppressing expression of MMPs, ADAMTS, NOX-4, generation of ROS, and activation of NF-κB via the IκBα/JNK/AP-1 pathway through targeted inhibition of CysLTR1. These findings suggest that zafirlukast possesses a protective effect against AGEs- induced damage and dysfunction in human chondrocytes.

Keywords

AGEs; Articular ECM; NF-κB; NOX-4; Osteoarthritis; Zafirlukast.

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