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Open AccessArticle

Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol

1
IRCCS Centro Neurolesi “Bonino Pulejo”, 98124 Messina, Italy
2
Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy
*
Author to whom correspondence should be addressed.
Medicina 2019, 55(11), 747; https://doi.org/10.3390/medicina55110747
Received: 26 September 2019 / Revised: 4 November 2019 / Accepted: 14 November 2019 / Published: 18 November 2019
(This article belongs to the Special Issue Use of Medicinal Cannabis and Synthetic Cannabinoids)
Background and Objectives: Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Materials and Methods: The motoneuron-like cell line NSC-34 differentiated by serum deprivation and with the additional treatment of all-trans retinoic acid (RA) is a valid model to investigate molecular events linked to neurodegeneration in ALS. Results: Pre-treatment with CBG (at 2.5 and 5 µM doses) alone and in combination with CBD (at 2.5 and 5 µM doses) was able to reduce neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In particular, the pre-treatment with CBD at a 5 µM dose decreased TNF-α levels and increased IL10 and IL-37 expression. CBG–CBD association at a 5 µM dose also reduced NF-kB nuclear factor activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a 5 µM dose decreased iNOS expression and increased Nrf2 levels. Furthermore, the pre-treatment with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-2 expression. Our data show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated. Conclusions: Our results provide preliminary support on the potential therapeutic application of a CBG–CBD combination for further preclinical studies. View Full-Text
Keywords: NSC-34 cells; amyotrophic lateral sclerosis (ALS); neuroinflammation; lipopolysaccharide (LPS); cannabigerol; cannabidiol NSC-34 cells; amyotrophic lateral sclerosis (ALS); neuroinflammation; lipopolysaccharide (LPS); cannabigerol; cannabidiol
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Mammana, S.; Cavalli, E.; Gugliandolo, A.; Silvestro, S.; Pollastro, F.; Bramanti, P.; Mazzon, E. Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol. Medicina 2019, 55, 747.

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