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

Endocannabinoid Research Group (ERG), Institute of Biomolecular Chemistry, National Research Council (ICB-CNR), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy

Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano 49, I-80131 Napoli, Italy

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Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy

Authors to whom correspondence should be addressed.

Molecules 2020, 25(5), 1119; https://doi.org/10.3390/molecules25051119

Received: 30 January 2020 / Revised: 28 February 2020 / Accepted: 1 March 2020 / Published: 3 March 2020

(This article belongs to the Special Issue Role of PPAR Receptors in Human Health and Disease)

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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. Altogether, these results candidate CBM as a novel bioactive compound potentially useful for the treatment of insulin resistance-related disorders. View Full-Text

Keywords: phytocannabinoids; cannabimovone (CBM); peroxisome proliferator-activated receptor gamma (PPARγ); molecular docking; molecular dynamics; insulin resistance

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MDPI and ACS Style

Iannotti, F.A.; De Maio, F.; Panza, E.; Appendino, G.; Taglialatela-Scafati, O.; De Petrocellis, L.; Amodeo, P.; Vitale, R.M. Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARγ Agonist via a Combined Computational and Functional Study. Molecules 2020, 25, 1119. https://doi.org/10.3390/molecules25051119

AMA Style

Iannotti FA, De Maio F, Panza E, Appendino G, Taglialatela-Scafati O, De Petrocellis L, Amodeo P, Vitale RM. Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARγ Agonist via a Combined Computational and Functional Study. Molecules. 2020; 25(5):1119. https://doi.org/10.3390/molecules25051119

Chicago/Turabian Style

Iannotti, Fabio A., Fabrizia De Maio, Elisabetta Panza, Giovanni Appendino, Orazio Taglialatela-Scafati, Luciano De Petrocellis, Pietro Amodeo, and Rosa M. Vitale. 2020. "Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARγ Agonist via a Combined Computational and Functional Study" Molecules 25, no. 5: 1119. https://doi.org/10.3390/molecules25051119

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

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