Journal Article

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

Mammana, Santa, Pollastro, Federica, Mazzon, Emanuela, Cavalli, Eugenio, Silvestro, Serena, Gugliandolo, Agnese, Bramanti, Placido

2019

Overview

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.

• Publisher: MDPI,MDPI AG
• Subject: amyotrophic lateral sclerosis (als) / cannabidiol / Cannabidiol - standards / Cannabidiol - therapeutic use / cannabigerol / Cannabinoids - standards / Cannabinoids - therapeutic use / Cell Culture Techniques - methods / Drug Therapy, Combination - methods / Drug Therapy, Combination - standards / Drug Therapy, Combination - statistics & numerical data / Humans / Inflammation - prevention & control / lipopolysaccharide (lps) / neuroinflammation / Neurons - drug effects / nsc-34 cells / Protective Factors