Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling.
Cannabis sativa L.
cannabidiol
inflammation
microglia
phytocomplex
β-Caryophyllene
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
revised:
27
12
2021
received:
13
06
2021
accepted:
12
01
2022
pubmed:
9
4
2022
medline:
25
5
2022
entrez:
8
4
2022
Statut:
ppublish
Résumé
Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD- and terpenes-enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV-2 microglial cells, compared with CBD and β-caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS-induced upregulation of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was significantly attenuated by CSE and only partially by CBD, whereas CAR was ineffective. In BV-2 cells, these anti-inflammatory effects exerted by CSE phytocomplex were only partially dependent on CB2r modulation and they were mediated by the regulation of enzymes responsible for the endocannabinoids metabolism, by the inhibition of reactive oxygen species release and the modulation of JNK/p38 cascade with consequent NF-κB p65 nuclear translocation suppression. Our data suggest that C. sativa phytocomplex and its multitarget mechanism could represent a novel therapeutic strategy for neuroinflammatory-related diseases.
Identifiants
pubmed: 35393641
doi: 10.1002/ptr.7458
pmc: PMC9325551
doi:
Substances chimiques
Cytokines
0
Endocannabinoids
0
Lipopolysaccharides
0
NF-kappa B
0
Receptor, Cannabinoid, CB2
0
Cannabidiol
19GBJ60SN5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2246-2263Informations de copyright
© 2022 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.
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