PMID- 35890124
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 15
IP  - 7
DP  - 2022 Jul 2
TI  - Dehydroisohispanolone as a Promising NLRP3 Inhibitor Agent: Bioevaluation and 
      Molecular Docking.
LID - 10.3390/ph15070825 [doi]
LID - 825
AB  - Dehydroisohispanolone (DIH), is a labdane diterpene that has exhibited 
      anti-inflammatory activity via inhibition of NF-kappaB 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-1beta 
      (IL-1beta) 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-1beta 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-1beta 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.
FAU - Gonzalez-Cofrade, Laura
AU  - Gonzalez-Cofrade L
AD  - Departamento de Farmacologia, Farmacognosia y Botanica, Facultad de Farmacia, 
      Universidad Complutense de Madrid (UCM), Plaza Ramon y Cajal s/n, 28040 Madrid, 
      Spain.
FAU - Cuadrado, Irene
AU  - Cuadrado I
AD  - Departamento de Farmacologia, Farmacognosia y Botanica, Facultad de Farmacia, 
      Universidad Complutense de Madrid (UCM), Plaza Ramon y Cajal s/n, 28040 Madrid, 
      Spain.
FAU - Amesty, Angel
AU  - Amesty A
AD  - Departamento de Quimica Organica, Instituto Universitario de Bio-Organica Antonio 
      Gonzalez, Universidad de La Laguna, Avda, Astrofisico Francisco Sanchez 2, 38206 
      La Laguna, Tenerife, Spain.
FAU - Estevez-Braun, Ana
AU  - Estevez-Braun A
AUID- ORCID: 0000-0001-5279-7099
AD  - Departamento de Quimica Organica, Instituto Universitario de Bio-Organica Antonio 
      Gonzalez, Universidad de La Laguna, Avda, Astrofisico Francisco Sanchez 2, 38206 
      La Laguna, Tenerife, Spain.
FAU - de Las Heras, Beatriz
AU  - de Las Heras B
AD  - Departamento de Farmacologia, Farmacognosia y Botanica, Facultad de Farmacia, 
      Universidad Complutense de Madrid (UCM), Plaza Ramon y Cajal s/n, 28040 Madrid, 
      Spain.
FAU - Hortelano, Sonsoles
AU  - Hortelano S
AUID- ORCID: 0000-0003-2528-0072
AD  - Unidad de Terapias Farmacologicas, Area de Genetica Humana, Instituto de 
      Investigacion de Enfermedades Raras (IIER), Instituto de Salud Carlos III, 
      Carretera de Majadahonda-Pozuelo Km 2, 28220 Madrid, Spain.
LA  - eng
GR  - PI17CIII/00012/Instituto de Salud Carlos III/
GR  - PI20CIII/00018/Instituto de Salud Carlos III/
GR  - RTI2018-094356-B-C21/Ministerio de Ciencia, Innovacion y Universidades (MICIU)/
GR  - Pro ID 2021010037/Agencia Canaria de Investigacion, Innovacion y Sociedad de la 
      Informacion/
GR  - FPU17/03519/Ministerio de Educacion Cultura y Deporte/
PT  - Journal Article
DEP - 20220702
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC9316970
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - caspase-1
OT  - dehydroisohispanolone
OT  - diterpene
OT  - interleukin-1beta
OT  - pyroptosis
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/02
CRDT- 2022/07/27 01:38
PHST- 2022/06/01 00:00 [received]
PHST- 2022/06/27 00:00 [revised]
PHST- 2022/06/28 00:00 [accepted]
PHST- 2022/07/27 01:38 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/02 00:00 [pmc-release]
AID - ph15070825 [pii]
AID - pharmaceuticals-15-00825 [pii]
AID - 10.3390/ph15070825 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2022 Jul 2;15(7):825. doi: 10.3390/ph15070825.