Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
Volume 67, Issue 2, Pages 27-40Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-20-0305
Keywords
gouty arthritis; cucurbitacin B; NLRP3; glycolysis
Categories
Funding
- Psychosomatic Medicine Project of Key Developing Disciplines of Shanghai Municipal Health Commission [2019ZB0202]
- National Natural Science Foundation of China [81974105, 81400834, 81500589, 81570799, 81670805]
- Shanghai Pujiang Program [2019PJD050]
- Cultivation project for National Natural Science Foundation of Shanghai Tongji Hospital
- Science and Technology Innovation Program of Shanghai [16411954700]
- Scientific research project of Shanghai Health Committee [20194Y0460]
- Novo Nordisk China Diabetes Young Scientific Talent Research Funding
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Cucurbitacin B has anti-inflammatory effects on gout by inhibiting NLRP3 inflammasome activation in macrophages, reducing IL-1 beta secretion, and ameliorating symptoms and inflammatory cell infiltration in a mouse model of gout arthritis.
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 upregulated caspase 1 protease and IL-1 beta 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 in a mouse model with MSU-induced acute gouty arthritis. Our results demonstrated that CuB effectively suppressed multiple stimuli-activated IL-1 beta 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 an NLRP3 inflammasome inhibitor with therapeutic potential for treating NLRP3 inflammasome-mediated diseases, especially gouty arthritis.
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