González Cofrade, LauraJ. P. GreenHeras Polo, Beatriz De LasTerencio, CarmenHortelano, SonsolesBrough, DavidEstévez-Braun, AnaFerrándiz, Laría LuisaCuadrado Berrocal, Irene2025-12-152025-12-152025-10-01González-Cofrade L, Green JP, De Las Heras B, Terencio MC, Hortelano S, Brough D, et al. Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis. Biochemical Pharmacology [Internet]. octubre de 2025 [citado 15 de diciembre de 2025];240:117114. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S000629522500379X10.1016/j.bcp.2025.117114https://hdl.handle.net/20.500.14352/128921Natural 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://dx.doi.org/10.1016/j.bcp.2025.117114open access615.01/.03DehydroisohispanoloneNLRP3 inflammasomeIL-1βASCMacrophagesGouty arthritisFarmacología (Farmacia)2302.30 Terpenos3209 Farmacología