2026-08-13T06:09:39Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/152422025-06-17T11:19:58Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
González-Cofrade, Laura
author
Cuadrado, Irene
author
Amesty, Ángel
author
Estévez-Braun, Ana
author
de Las Heras, Beatriz
author
Hortelano, Sonsoles
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Agencia Canaria de Investigación, Innovación y Sociedad de la Información
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Gobierno de Canarias (España)
2022-11-29T13:20:43Z
2022-11-29T13:20:43Z
2022-07-02
Pharmaceuticals (Basel). 2022 Jul 2;15(7):825.
10.3390/ph15070825
1424-8247
Pharmaceuticals (Basel, Switzerland)
35890124
http://hdl.handle.net/20.500.12105/15242
Dehydroisohispanolone (DIH), is a labdane diterpene that has exhibited anti-inflammatory activity via inhibition of NF-κB activation, although its potential effects on inflammasome activation remain unexplored. This study aims to elucidate whether DIH modulates NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in macrophages. Our findings show that DIH inhibited NLRP3 activation triggered by Nigericin (Nig), adenosine triphosphate (ATP) and monosodium urate (MSU) crystals, indicating broad inhibitory effects. DIH significantly attenuated caspase-1 activation and secretion of the interleukin-1β (IL-1β) in J774A.1 cells. Interestingly, the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), pro-caspase-1 and pro-IL-1β were not affected by DIH treatment. Furthermore, we found that DIH pretreatment also inhibited the lipopolysaccharide (LPS)-induced NLRP3 inflammasome priming stage. In addition, DIH alleviated pyroptosis mediated by NLRP3 inflammasome activation. Similar results on IL-1β release were observed in Nig-activated bone marrow-derived macrophages (BMDMs). Covalent molecular docking analysis revealed that DIH fits well into the ATP-binding site of NLRP3 protein, forming a covalent bond with Cys415. In conclusion, our experiments show that DIH is an effective NLRP3 inflammasome inhibitor and provide new evidence for its application in the therapy of inflammation-related diseases.
eng
NLRP3 inflammasome
Caspase-1
Dehydroisohispanolone.
Diterpene
Interleukin-1β
Pyroptosis
Dehydroisohispanolone as a Promising NLRP3 Inhibitor Agent: Bioevaluation and Molecular Docking
research article
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DehydroisohispanoloneAsAPromising_2022.pdf
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DehydroisohispanoloneAsAPromisingSupplementaryMaterials_2022.pdf
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DehydroisohispanoloneAsAPromising_2022.pdf.txt
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