title: A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis.
abstract: Phytocannabinoids like ∆(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms. Natural and synthetic cannabinoids also target the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ), an attractive molecular target for the treatment of neuroinflammation. As part of a study on the SAR of phytocannabinoids, we have investigated the effect of the oxidation modification in the resorcinol moiety of cannabigerol (CBG) on CB(1), CB(2) and PPARγ binding affinities, identifying cannabigerol quinone (VCE-003) as a potent anti-inflammatory agent. VCE-003 protected neuronal cells from excitotoxicity, activated PPARγ transcriptional activity and inhibited the release of pro-inflammatory mediators in LPS-stimulated microglial cells. Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS) was used to investigate the anti-inflammatory activity of this compound in vivo. Motor function performance was evaluated and the neuroinflammatory response and gene expression pattern in brain and spinal cord were studied by immunostaining and qRT-PCR. We found that VCE-003 ameliorated the symptoms associated to TMEV infection, decreased microglia reactivity and modulated the expression of genes involved in MS pathophysiology. These data lead us to consider VCE-003 to have high potential for drug development against MS and perhaps other neuroinflammatory diseases.
authors.affiliation: Vivacell Biotechnology España S.L. Parque Científico Tecnológico Rabanales 21, c/Cecilia Payne, Parcela ID 8.1, 14014, Córdoba, Spain.
authors.forename: Aitor G
authors.initials: AG
authors.lastname: Granja
authors.forename: Francisco
authors.initials: F
authors.lastname: Carrillo-Salinas
authors.forename: Alberto
authors.initials: A
authors.lastname: Pagani
authors.forename: María
authors.initials: M
authors.lastname: Gómez-Cañas
authors.forename: Roberto
authors.initials: R
authors.lastname: Negri
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarrete
authors.forename: Miriam
authors.initials: M
authors.lastname: Mecha
authors.forename: Leyre
authors.initials: L
authors.lastname: Mestre
authors.forename: Bend L
authors.initials: BL
authors.lastname: Fiebich
authors.forename: Irene
authors.initials: I
authors.lastname: Cantarero
authors.forename: Marco A
authors.initials: MA
authors.lastname: Calzado
authors.forename: Maria L
authors.initials: ML
authors.lastname: Bellido
authors.forename: Javier
authors.initials: J
authors.lastname: Fernandez-Ruiz
authors.forename: Giovanni
authors.initials: G
authors.lastname: Appendino
authors.forename: Carmen
authors.initials: C
authors.lastname: Guaza
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000627:therapeutic use*; D018188:Cardiovirus Infections / Q000188:drug therapy / Q000473:pathology; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000378:metabolism; D011247:Pregnancy; D011597:Psychomotor Performance / Q000502:physiology; D011809:Quinones / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D017945:Theilovirus; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D002186:Cannabinoids; D016207:Cytokines; D018696:Neuroprotective Agents; D047495:PPAR gamma; D011809:Quinones; C581223:VCE-003; D019010:Vascular Cell Adhesion Molecule-1; D007770:L-Lactate Dehydrogenase; C037036:cannabigerol; D015232:Dinoprostone