RT Journal Article
T1 Dehydroisohispanolone as a promising NLRP3 inhibitor agent: bioevaluation and molecular docking
A1 González Cofrade, Laura
A1 Cuadrado Berrocal, Irene
A1 Heras Polo, Beatriz De Las
A1 Angel Amesty, 
A1 Ana Estevez-Braun, 
A1 Sonsoles Hortelano, 
AB 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.
PB MDPI
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/118830
UL https://hdl.handle.net/20.500.14352/118830
LA eng
NO González-Cofrade L, Cuadrado I,   Amesty A,  Estévez-Braun  A,  de Las Heras B,  Hortelano  S. Dehydroisohispanolone as a Promising NLRP3 Inhibitor Agent: Bioevaluation and Molecular Docking. Pharmaceuticals (Basel) . 2022 Jul 2;15(7):825
NO Instituto de Salud Carlos III (España)
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Ministerio de Educación, Cultura y Deporte (España)
NO Agencia Canaria de Investigación, Innovación y Sociedad de la Información
NO Federación Española de Enfermedades Raras
NO European Commission
NO Cabildo de Tenerife
DS Docta Complutense
RD 21 abr 2025