Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa , as a Novel PPARγ Agonist via a Combined Computational and Functional Study

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Fabio Arturo IannottiRosa Maria Vitale

Abstract

Phytocannabinoids (pCBs) are a large family of meroterpenoids isolated from the plant Cannabis sativa. Δ9-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 (PPARγ), a nuclear receptor involved in energy homeostasis and lipid metabolism. In the search of new pCBs potentially acting as PPARγ agonists, we identified cannabimovone (CBM), a structurally unique abeo-menthane pCB, as a novel PPARγ modulator via a combined computational and experimental approach. The ability of CBM to act as dual PPARγ/α 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 PPARγ. Luciferase assays confirmed the computational results, showing a selective activation of PPARγ by CBM in the low micromolar range. CBM promoted the expression of PPARγ target genes regulating the adipocyte differentiation and prevented palmitate-induced insulin signaling impairment. A...Continue Reading

References

Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K L GearingJ A Gustafsson
May 26, 2001·The Journal of Clinical Investigation·M Mueckler
Jun 8, 2001·Annual Review of Biochemistry·T M WillsonS A Kliewer
Jan 10, 2002·Genes & Development·Evan D RosenBruce M Spiegelman
Jan 31, 2002·Annual Review of Medicine·Joel Berger, David E Moller
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 28, 2005·Diabetes·Bart Staels, Jean-Charles Fruchart
Aug 8, 2006·ChemMedChem·John T MooreKenneth H Pearce
May 23, 2007·The New England Journal of Medicine·Steven E Nissen, Kathy Wolski
Apr 1, 2009·The Journal of Biological Chemistry·Seiji NakamuraShuichi Kaneko
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Dec 31, 2009·The Journal of Pharmacology and Experimental Therapeutics·Fabio Arturo IannottiMaurizio Taglialatela
Jan 17, 2012·Current Topics in Medicinal Chemistry·Andreea CiudinRafael Simó
May 15, 2012·Journal of Chemical Theory and Computation·Andreas W GötzRoss C Walker
Jul 13, 2012·Bioscience, Biotechnology, and Biochemistry·Xiao-Tao FengWen-Jian Wang
Dec 3, 2014·Diabetes & Metabolic Syndrome·C Janani, B D Ranjitha Kumari
Aug 13, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Clementino Ibeas BihBenjamin J Whalley
Sep 4, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Orrin DevinskyVincenzo Di Marzo
Jan 23, 2016·International Journal of Molecular Sciences·Dorothy MosetiWoo-Kyun Kim
Apr 15, 2016·British Journal of Pharmacology·Saoirse Elizabeth O'Sullivan
Oct 11, 2016·Natural Product Reports·Lumír Ondřej HanušGiovanni Appendino
Sep 7, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Douglas L BoggsMohini Ranganathan

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Methods Mentioned

BETA
PCR
Assay
Protein Assay

Software Mentioned

Clust2
GAMESS
AutoDock Tools ( ADT )
Tripos
Quantity
dbscan
one
Autodock
Ghemical
AMBER

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