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Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus

1
Department of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, Italy
2
Genetic Molecular Institute of CNR, Unit of Chieti, “G. d’ Annunzio” University, Via dei Vestini 31, 66100 Chieti-Pescara, Italy
3
Department of Medicine and Ageing Sciences, “G. d’ Annunzio” University, Via dei Vestini 31, 66100 Chieti-Pescara, Italy.
*
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(1), 71; https://doi.org/10.3390/antiox9010071
Received: 9 December 2019 / Revised: 23 December 2019 / Accepted: 10 January 2020 / Published: 13 January 2020
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
Background: Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite although there are no studies elucidating their role in the hypothalamic appetite-regulating network. Consequently, the aim of the present research is to investigate the role of CBD and CBG in regulating hypothalamic neuromodulators. Comparative evaluations between oxidative stress and food intake-modulating mediators were also performed. Methods: Rat hypothalamic Hypo-E22 cells and isolated tissues were exposed to either CBD or CBG, and the gene expressions of neuropeptide (NP)Y, pro-opiomelanocortin (POMC) and fatty acid amide hydrolase were assessed. In parallel, the influence of CBD on the synthesis and release of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) was evaluated. The 3-hydroxykinurenine/kinurenic acid (3-HK/KA) ratio was also determined. Results: Both CBD and CBG inhibited NPY and POMC gene expression and decreased the 3-HK/KA ratio in the hypothalamus. The same compounds also reduced hypothalamic NE synthesis and DA release, whereas the sole CBD inhibited 5-HT synthesis. Conclusion: The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways. View Full-Text
Keywords: cannabidiol; cannabigerol; hypothalamus; neurotransmitter; neuropeptide; kinurenine pathway cannabidiol; cannabigerol; hypothalamus; neurotransmitter; neuropeptide; kinurenine pathway
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di Giacomo, V.; Chiavaroli, A.; Orlando, G.; Cataldi, A.; Rapino, M.; Di Valerio, V.; Leone, S.; Brunetti, L.; Menghini, L.; Recinella, L.; Ferrante, C. Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus. Antioxidants 2020, 9, 71.

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