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Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARgamma Agonist via a Combined Computational and Functional Study
- Source :
- Molecules (Basel, Online) 25 (2020). doi:10.3390/molecules25051119, info:cnr-pdr/source/autori:Iannotti F.A.; De Maio F.; Panza E.; Appendino G.; Taglialatela-Scafati O.; De Petrocellis L.; Amodeo P.; Vitale R.M./titolo:Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARgamma Agonist via a Combined Computational and Functional Study/doi:10.3390%2Fmolecules25051119/rivista:Molecules (Basel, Online)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:25, Molecules, Vol 25, Iss 5, p 1119 (2020), Molecules, Volume 25, Issue 5
- Publication Year :
- 2020
- Publisher :
- Molecules/MDPI, Molecular Diversity Preservation International, Basel, 2020.
-
Abstract
- Phytocannabinoids (pCBs) are a large family of meroterpenoids isolated from the plant Cannabis sativa. &Delta<br />9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best investigated phytocannabinoids due to their relative abundance and interesting bioactivity profiles. In addition to various targets, THC and CBD are also well-known agonists of peroxisome proliferator-activated receptor gamma (PPAR&gamma<br />), a nuclear receptor involved in energy homeostasis and lipid metabolism. In the search of new pCBs potentially acting as PPAR&gamma<br />agonists, we identified cannabimovone (CBM), a structurally unique abeo-menthane pCB, as a novel PPAR&gamma<br />modulator via a combined computational and experimental approach. The ability of CBM to act as dual PPAR&gamma<br />/&alpha<br />agonist was also evaluated. Computational studies suggested a different binding mode toward the two isoforms, with the compound able to recapitulate the pattern of H-bonds of a canonical agonist only in the case of PPAR&gamma<br />Luciferase assays confirmed the computational results, showing a selective activation of PPAR&gamma<br />by CBM in the low micromolar range. CBM promoted the expression of PPAR&gamma<br />target genes regulating the adipocyte differentiation and prevented palmitate-induced insulin signaling impairment. Altogether, these results candidate CBM as a novel bioactive compound potentially useful for the treatment of insulin resistance-related disorders.
- Subjects :
- Agonist
PPARgamma
PPARs
cannabimovone
medicine.drug_class
medicine.medical_treatment
peroxisome proliferator-activated receptor gamma (pparĪ³)
Pharmaceutical Science
Pharmacology
Molecular dynamics
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
0302 clinical medicine
Molecular docking, molecular dynamics, insulin resistance
cannabimovone (cbm)
lcsh:Organic chemistry
insulin resistance
Drug Discovery
medicine
Luciferase
Physical and Theoretical Chemistry
phytocannabinoids
Receptor
030304 developmental biology
0303 health sciences
biology
Chemistry
Organic Chemistry
Lipid metabolism
Insulin receptor
Nuclear receptor
Chemistry (miscellaneous)
Molecular docking
biology.protein
Molecular Medicine
Cannabinoid
Phytocannabinoids, cannabimovone (CBM)
Cannabidiol
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Molecules (Basel, Online) 25 (2020). doi:10.3390/molecules25051119, info:cnr-pdr/source/autori:Iannotti F.A.; De Maio F.; Panza E.; Appendino G.; Taglialatela-Scafati O.; De Petrocellis L.; Amodeo P.; Vitale R.M./titolo:Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARgamma Agonist via a Combined Computational and Functional Study/doi:10.3390%2Fmolecules25051119/rivista:Molecules (Basel, Online)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:25, Molecules, Vol 25, Iss 5, p 1119 (2020), Molecules, Volume 25, Issue 5
- Accession number :
- edsair.doi.dedup.....e0544a5511a5ff04fc924b2c522f8d5e