Therapeutic Potential of Phytocannabinoid Cannabigerol for Multiple Sclerosis: Modulation of Microglial Activation In Vitro and In Vivo

Sigal Fleisher-Berkovich, Yvonne Ventura, Maya Amoyal, Arik Dahan, Valeria Feinshtein, Leenor Alfahel, Adrian Israelson, Nirit Bernstein, Jonathan Gorelick, Shimon Ben-Shabat

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Multiple sclerosis (MS) is a widespread chronic neuroinflammatory and neurodegenerative disease. Microglia play a crucial role in the pathogenesis of MS via the release of cytokines and reactive oxygen species, e.g., nitric oxide. Research involving the role of phytocannabinoids in neuroinflammation is currently receiving much attention. Cannabigerol is a main phytocannabinoid, which has attracted significant pharmacological interest due to its non-psychotropic nature. In this research, we studied the effects of cannabigerol on microglial inflammation in vitro, followed by an in vivo study. Cannabigerol attenuated the microglial production of nitric oxide in BV2 microglia and primary glial cells; concomitant treatment of the cells with cannabigerol and telmisartan (a neuroprotective angiotensin receptor blocker) decreased nitric oxide production additively. Inducible nitric oxide synthase (iNOS) expression was also reduced by cannabigerol. Moreover, tumor necrosis factor-α (TNF-α), a major cytokine involved in MS, was significantly reduced by cannabigerol in both cell cultures. Next, we studied the effects of cannabigerol in vivo using a mice model of MS, experimental autoimmune encephalomyelitis (EAE). The clinical scores of EAE mice were attenuated upon cannabigerol treatment; additionally, lumbar sections of EAE mice showed enhanced neuronal loss (relative to control mice), which was restored by cannabigerol treatment. Altogether, the set of experiments presented in this work indicates that cannabigerol possesses an appealing therapeutic potential for the treatment of MS.

Original languageEnglish
Article number376
JournalBiomolecules
Volume13
Issue number2
DOIs
StatePublished - 1 Feb 2023

Keywords

  • EAE
  • cannabigerol
  • lipopolysaccharide neuroinflammation
  • microglia
  • nitric oxide

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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