NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice

in Journal of Molecular Endocrinology
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  • 1 Y Xue, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 2 R Li, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 3 P Fang, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 4 Z Ye, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 5 Y Zhao, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 6 Y Zhou, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 7 K Zhang, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • 8 L Li, Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China

Correspondence: Ling Li, Email: dalingll@126.com

Gouty arthritis is a common inflammatory disease characterized by monosodium urate (MSU) crystal induced nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation with up-regulated caspase-1 protease and IL-1β in macrophages. Cucurbitacin B (CuB) is a tetracyclic triterpene that possesses a potential anti-inflammatory activity. However, the immunomodulatory and anti-inflammatory effects of CuB on gout have not been well characterized. Therefore, the purpose of the present study was to determine whether CuB exhibits anti-inflammatory effects on gout and to analyze the underlying molecular mechanism. We examined the effects of CuB on various stimuli-activated bone marrow-derived macrophages (BMDMs) and the mice model with MSU-induced acute gouty arthritis. Our results demonstrated that CuB effectively suppressed multiple stimuli-activated IL-1β secretion by interrupting NLRP3 inflammasome complex formation, inhibiting NLRP3 inflammasome activation and suppressing key enzymes of glycolysis in macrophages. Consistent with this, CuB pretreatment also ameliorated MSU-induced arthritis in vivo models of gout arthritis, manifested by reduced foot swelling and inflammatory cell infiltration. Taken together, our data provide the evidence that CuB is a NLRP3 inflammasome inhibitor with therapeutic potential for treating NLRP3 inflammasome-mediated diseases, especially gouty arthritis.

 

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