Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis

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 infl...

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Autores: González Cofrade, Laura, J. P. Green, Heras Polo, Beatriz De Las, Terencio, Carmen, Hortelano, Sonsoles, Brough, David, Estévez-Braun, Ana, Ferrándiz, Laría Luisa, Cuadrado Berrocal, Irene
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/128921
Acesso em linha:https://hdl.handle.net/20.500.14352/128921
Access Level:acceso abierto
Palavra-chave:615.01/.03
Dehydroisohispanolone
NLRP3 inflammasome
IL-1β
ASC
Macrophages
Gouty arthritis
Farmacología (Farmacia)
2302.30 Terpenos
3209 Farmacología
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oai_identifier_str oai:docta.ucm.es:20.500.14352/128921
network_acronym_str ES
network_name_str España
repository_id_str
spelling Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritisGonzález Cofrade, LauraJ. P. GreenHeras Polo, Beatriz De LasTerencio, CarmenHortelano, SonsolesBrough, DavidEstévez-Braun, AnaFerrándiz, Laría LuisaCuadrado Berrocal, Irene615.01/.03DehydroisohispanoloneNLRP3 inflammasomeIL-1βASCMacrophagesGouty arthritisFarmacología (Farmacia)2302.30 Terpenos3209 FarmacologíaNatural 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.Universidad Complutense de Madrid20252025-10-0120252025-10-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/128921reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-124890OB-I00 ESTRATEGIAS DE DIAGNOSTICO Y TRATAMIENTO EN ENFERMEDADES INFLAMATORIAS CRONICAS ARTICULARES Y DE LA PIELopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1289212026-06-02T12:44:21Z
dc.title.none.fl_str_mv Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
title Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
spellingShingle Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
González Cofrade, Laura
615.01/.03
Dehydroisohispanolone
NLRP3 inflammasome
IL-1β
ASC
Macrophages
Gouty arthritis
Farmacología (Farmacia)
2302.30 Terpenos
3209 Farmacología
title_short Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
title_full Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
title_fullStr Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
title_full_unstemmed Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
title_sort Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
dc.creator.none.fl_str_mv González Cofrade, Laura
J. P. Green
Heras Polo, Beatriz De Las
Terencio, Carmen
Hortelano, Sonsoles
Brough, David
Estévez-Braun, Ana
Ferrándiz, Laría Luisa
Cuadrado Berrocal, Irene
author González Cofrade, Laura
author_facet González Cofrade, Laura
J. P. Green
Heras Polo, Beatriz De Las
Terencio, Carmen
Hortelano, Sonsoles
Brough, David
Estévez-Braun, Ana
Ferrándiz, Laría Luisa
Cuadrado Berrocal, Irene
author_role author
author2 J. P. Green
Heras Polo, Beatriz De Las
Terencio, Carmen
Hortelano, Sonsoles
Brough, David
Estévez-Braun, Ana
Ferrándiz, Laría Luisa
Cuadrado Berrocal, Irene
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 615.01/.03
Dehydroisohispanolone
NLRP3 inflammasome
IL-1β
ASC
Macrophages
Gouty arthritis
Farmacología (Farmacia)
2302.30 Terpenos
3209 Farmacología
topic 615.01/.03
Dehydroisohispanolone
NLRP3 inflammasome
IL-1β
ASC
Macrophages
Gouty arthritis
Farmacología (Farmacia)
2302.30 Terpenos
3209 Farmacología
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-10-01
2025
2025-10-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/128921
url https://hdl.handle.net/20.500.14352/128921
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-124890OB-I00 ESTRATEGIAS DE DIAGNOSTICO Y TRATAMIENTO EN ENFERMEDADES INFLAMATORIAS CRONICAS ARTICULARES Y DE LA PIEL
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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