Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Cannabidiol (CBD) and cannabigerol (CBG) are <i>Cannabis sativa</i> terpenophenols. Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experim...

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Main Authors: Viviana di Giacomo, Annalisa Chiavaroli, Lucia Recinella, Giustino Orlando, Amelia Cataldi, Monica Rapino, Valentina Di Valerio, Maurizio Ronci, Sheila Leone, Luigi Brunetti, Luigi Menghini, Gokhan Zengin, Gunes Ak, Hassan H. Abdallah, Claudio Ferrante
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/10/3575
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author Viviana di Giacomo
Annalisa Chiavaroli
Lucia Recinella
Giustino Orlando
Amelia Cataldi
Monica Rapino
Valentina Di Valerio
Maurizio Ronci
Sheila Leone
Luigi Brunetti
Luigi Menghini
Gokhan Zengin
Gunes Ak
Hassan H. Abdallah
Claudio Ferrante
author_facet Viviana di Giacomo
Annalisa Chiavaroli
Lucia Recinella
Giustino Orlando
Amelia Cataldi
Monica Rapino
Valentina Di Valerio
Maurizio Ronci
Sheila Leone
Luigi Brunetti
Luigi Menghini
Gokhan Zengin
Gunes Ak
Hassan H. Abdallah
Claudio Ferrante
author_sort Viviana di Giacomo
collection DOAJ
description Cannabidiol (CBD) and cannabigerol (CBG) are <i>Cannabis sativa</i> terpenophenols. Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K<sup>+</sup> 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. <i>Conclusion:</i> The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.
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spelling doaj.art-4def1f0cc2d741f69dd4c1b89cb833dd2023-11-20T00:53:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110357510.3390/ijms21103575Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated CortexesViviana di Giacomo0Annalisa Chiavaroli1Lucia Recinella2Giustino Orlando3Amelia Cataldi4Monica Rapino5Valentina Di Valerio6Maurizio Ronci7Sheila Leone8Luigi Brunetti9Luigi Menghini10Gokhan Zengin11Gunes Ak12Hassan H. Abdallah13Claudio Ferrante14Department of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyGenetic Molecular Institute of CNR, Unit of Chieti, “G. d’ Annunzio” University, Via dei Vestini 31, 66100 Chieti-Pescara, ItalyDepartment of Medicine and Ageing Sciences, “G. d’ Annunzio” University, Via dei Vestini 31, 66100 Chieti-Pescara, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyDepartment of Biology, Science Faculty, Selcuk University, Campus, 42130 Konya, TurkeyDepartment of Biology, Science Faculty, Selcuk University, Campus, 42130 Konya, TurkeyChemistry Department, College of Education, Salahaddin University-Erbil, Erbil 44001, IraqDepartment of Pharmacy, Università degli Studi “Gabriele d’Annunzio”, via dei Vestini 31, 66100 Chieti, ItalyCannabidiol (CBD) and cannabigerol (CBG) are <i>Cannabis sativa</i> terpenophenols. Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K<sup>+</sup> 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. <i>Conclusion:</i> The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.https://www.mdpi.com/1422-0067/21/10/3575cannabidiolcannabigerolneuroprotectionserotoninapoptosisproteomic analysis
spellingShingle Viviana di Giacomo
Annalisa Chiavaroli
Lucia Recinella
Giustino Orlando
Amelia Cataldi
Monica Rapino
Valentina Di Valerio
Maurizio Ronci
Sheila Leone
Luigi Brunetti
Luigi Menghini
Gokhan Zengin
Gunes Ak
Hassan H. Abdallah
Claudio Ferrante
Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
International Journal of Molecular Sciences
cannabidiol
cannabigerol
neuroprotection
serotonin
apoptosis
proteomic analysis
title Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
title_full Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
title_fullStr Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
title_full_unstemmed Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
title_short Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes
title_sort antioxidant and neuroprotective effects induced by cannabidiol and cannabigerol in rat ctx tna2 astrocytes and isolated cortexes
topic cannabidiol
cannabigerol
neuroprotection
serotonin
apoptosis
proteomic analysis
url https://www.mdpi.com/1422-0067/21/10/3575
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