2026-06-14T03:33:40Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/273842026-04-01T00:18:21Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc González-Cofrade, Laura author Green, Jack P author de Las Heras, Beatriz author Terencio, María Carmen author Hortelano, Sonsoles author Brough, David author Estévez-Braun, Ana author Ferrándiz, María Luisa author Cuadrado, Irene author 2025-10 Natural products constitute an important resource for drug discovery with hispanolone derivatives recognized as bioactive diterpenes due to their broad therapeutic potential. Dehydroisohispanolone (DIH) is an anti-inflammatory labdane diterpene, that acts as a multi-target agent through various inflammation pathways. Aberrant activation of the Nod-like receptor protein 3 (NLRP3) inflammasome is involved in several inflammatory diseases, including gout. This study explores the mechanisms underlying the effects of DIH on the NLRP3 inflammasome and pyroptosis in vitro and evaluates its therapeutic effects on gouty arthritis in mice. DIH suppresses interleukin (IL)-1β secretion and pyroptosis in lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages (BMDMs) elicited by broad stimuli. DIH exerts its action by disrupting adaptor apoptosis-associated speck-like protein (ASC) oligomerization, thereby inhibiting the assembly of inflammasome complex. Notably, DIH specifically inhibits NLRP3 inflammasome activation in murine BMDMs without affecting the absent in melanoma-2 (AIM2) or NOD-like receptor family CARD domain containing 4 (NLRC4) inflammasomes. In animal models, DIH significantly mitigated monosodium urate (MSU)-induced joint inflammation, reducing cytokine levels and myeloperoxidase (MPO) secretion. Overall, this study identified DIH as a specific inhibitor of the NLRP3 inflammasome, providing new insights into its potential as a therapeutic agent for NLRP3-mediated inflammatory diseases. González-Cofrade L, Green JP, de Las Heras B, Terencio MC, Hortelano S, Brough D, Estévez-Braun A, Ferrándiz ML, Cuadrado I. Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis. Biochem Pharmacol. 2025 Oct;240:117114. doi: 10.1016/j.bcp.2025.117114. Epub 2025 Jul 5. PMID: 40619011. 10.1016/j.bcp.2025.117114 Biochemical Pharmacology 40619011 https://hdl.handle.net/20.500.12105/27384 ASC Dehydroisohispanolone Gouty arthritis IL-1β Macrophages NLRP3 inflammasome Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis.