2026-06-14T03:32:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/273842026-04-01T00:18:21Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
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
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Agencia Estatal de Investigación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
2026-03-31T15:59:54Z
2026-03-31T15:59:54Z
2025-10
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
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.
eng
ASC
Dehydroisohispanolone
Gouty arthritis
IL-1β
Macrophages
NLRP3 inflammasome
Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis.
research article
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