ReferenceID 4998
NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice
J Mol Endocrinol
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) inflam
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- Reference Id
- 4998
- Evidence Id
- 21588
- Core Evidence Id
- 21588
- Source Reference Id
- 3243
- Herb2 Reference Id
- HBREF004040
- Subject Paper Key
- HBIN021843_34047713
- Pubmed Id
- 34047713
- Doi
- 10.1530/JME-20-0305
- Paper Title
- NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice
- Paper Abstract
- 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-1beta 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-1beta 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.
- Journal
- J Mol Endocrinol
- Publish Year
- 2021
- Experiment Subject
- mouse; stimuli-activated bone marrow-derived macrophages
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Foot Swelling; Gouty Arthritis; Inflammatory Cell Infiltration; Nlrp3 Inflammasome-mediated Diseases; Gout Arthritis; Arthritis; Msu-induced Acute Gouty Arthritis; Inflammatory Disease; Gout
- Paper Title Cn
- Paper Title En
- NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice
- Bilingual Status
- semi_complete