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Article

Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes

1
Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
2
European Center for Brain Research (CERC)/Santa Lucia Foundation IRCCS, 00143 Rome, Italy
3
Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy
4
Department of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, Italy
5
InMed Pharmaceuticals Inc., Vancouver, BC V6C 1B4, Canada
6
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Raffaele Capasso
Int. J. Mol. Sci. 2022, 23(10), 5430; https://doi.org/10.3390/ijms23105430
Received: 20 April 2022 / Revised: 6 May 2022 / Accepted: 11 May 2022 / Published: 12 May 2022
(This article belongs to the Special Issue New Insight into Cannabinoid Effects)
The decriminalization and legalization of cannabis has paved the way for investigations into the potential of the use of phytocannabinoids (pCBs) as natural therapeutics for the treatment of human diseases. This growing interest has recently focused on rare (less abundant) pCBs that are non-psychotropic compounds, such as cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) and cannabigerolic acid (CBGA). Notably, pCBs can act via the endocannabinoid system (ECS), which is involved in the regulation of key pathophysiological processes, and also in the skin. In this study, we used human keratinocytes (HaCaT cells) as an in vitro model that expresses all major ECS elements in order to systematically investigate the effects of CBG, CBC, THCV and CBGA. To this end, we analyzed the gene and protein expression of ECS components (receptors: CB1, CB2, GPR55, TRPV1 and PPARα/γ/δ; enzymes: NAPE-PLD, FAAH, DAGLα/β and MAGL) using qRT-PCR and Western blotting, along with assessments of their functionality using radioligand binding and activity assays. In addition, we quantified the content of endocannabinoid(-like) compounds (AEA, 2-AG, PEA, etc.) using UHPLC-MS/MS. Our results demonstrated that rare pCBs modulate the gene and protein expression of distinct ECS elements differently, as well as the content of endocannabinoid(-like) compounds. Notably, they all increased CB1/2 binding, TRPV1 channel stimulation and FAAH and MAGL catalytic activity. These unprecedented observations should be considered when exploring the therapeutic potential of cannabis extracts for the treatment of human skin diseases. View Full-Text
Keywords: endocannabinoids; enzymes; keratinocytes; phytocannabinoids; receptors; skin endocannabinoids; enzymes; keratinocytes; phytocannabinoids; receptors; skin
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MDPI and ACS Style

Di Meo, C.; Tortolani, D.; Standoli, S.; Angelucci, C.B.; Fanti, F.; Leuti, A.; Sergi, M.; Kadhim, S.; Hsu, E.; Rapino, C.; Maccarrone, M. Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes. Int. J. Mol. Sci. 2022, 23, 5430. https://doi.org/10.3390/ijms23105430

AMA Style

Di Meo C, Tortolani D, Standoli S, Angelucci CB, Fanti F, Leuti A, Sergi M, Kadhim S, Hsu E, Rapino C, Maccarrone M. Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes. International Journal of Molecular Sciences. 2022; 23(10):5430. https://doi.org/10.3390/ijms23105430

Chicago/Turabian Style

Di Meo, Camilla, Daniel Tortolani, Sara Standoli, Clotilde Beatrice Angelucci, Federico Fanti, Alessandro Leuti, Manuel Sergi, Salam Kadhim, Eric Hsu, Cinzia Rapino, and Mauro Maccarrone. 2022. "Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes" International Journal of Molecular Sciences 23, no. 10: 5430. https://doi.org/10.3390/ijms23105430

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