Phytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in
CNS diseases. A
cannabigerol quinone, the compound
VCE-003, has been shown to alleviate symptoms in a viral model of
multiple sclerosis (MS). Hence, we studied T cells and macrophages as targets for
VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and
cytokine and
chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of
VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype.
Experimental autoimmune encephalomyelitis (EAE) was induced by
myelin oligodendrocyte glycoprotein (MOG₃₅₋₅₅) immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that
VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Rα and
ICAM-1 activation markers in human primary T cells.
VCE-003 inhibits the secretion of Th1/Th17
cytokines and
chemokines in primary murine T cells, and it reduces the transcriptional activity of the
IL-2,
IL-17 and TNFα promoters induced by CD3/CD28. In addition,
VCE-003 and
JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile.
VCE-003 also prevented LPS-induced iNOS expression in microglia.
VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARγ receptor activation. A reduction in cell infiltrates, mainly CD4+ T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the therapeutic potential of
VCE-003 as an agent for the treatment of human
immune diseases with both inflammatory and autoimmune components.