Arthritis Rheumatol: Directly combined with the NLRP3 hot protein domain is a new way to prevent NLRP3 from driving inflammation and gout arthritis

The NLR family contains hot protein domain protein 3 (NLRP3) inflammatory small body and a variety of inflammatory diseases of the pathological physiology of the close relationshipThe study aims to identify small molecules that bind directly to NLRP3 to establish pharmacological treatments for NLRP3-associated diseasesperformed a structure-based virtual screening analysis of approximately 62,800 compounds to select effective NLRP3 inhibitorsThe production of caspase-1 (p10) and IL-1 beta was detected by immunoprinting and enzymatic immunoadsorption assays (ELISA) to analyze the activation of the inflammatory small body of NLRP3Inviva experiments were conducted using two gout arthritis models and an air bag inflammation model induced by injection of MSU crystalsThe human correlation was determined using primary sliding membrane fluid cells from gout patientsbeta-carotene (pre-vitamin A) inhibited nlRP3 itisary reactivation (p 05) induced by various activators (including MSU crystals) in primary macrophages of bone marrow-derived miceThe surface isometric meta-analysis showed that beta-carotene was directly bound to the hot protein domain (PYD) of NLRP3 (KD-3.41E-06)Molecular modeling and mutation analysis reveal patterns of interaction between beta-carotene and NLRP3 PYDIn the gout arthritis mouse model, oral beta-carotene can reduce the inflammatory symptoms (p0.05) induced by MSU crystals, which is associated with the suppression of the NLRP3 inflammatory body in inflammatory tissueIn addition, beta-carotene reduces IL-1 beta secretion (p0.05) of human fluid cells isolated from gout patients, demonstrating its inhibition of human cellsthe results show that beta-carotene is the selector and direct inhibitor of NLRP3, and that binding with NLRP3 PYD is a new pharmacological strategy to fight NLRP3 inflammatory small body-driven disease, including gout arthritis