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Therapeutic Potential of Phytocannabinoid Cannabigerol for Multiple Sclerosis: Modulation of Microglial Activation In
Sigal Fleisher-Berkovich1, Yvonne Ventura1, Maya Amoyal1
1Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
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.
Insights
Cannabigerol (CBG) reduces neuroinflammation in multiple sclerosis models. This non-psychotropic phytocannabinoid decreased nitric oxide and TNF-α in microglia and improved outcomes in experimental autoimmune encephalomyelitis mice.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease.
- Microglia are key players in MS pathogenesis, releasing inflammatory mediators like nitric oxide.
- Phytocannabinoids, particularly non-psychotropic ones like cannabigerol (CBG), are gaining attention for their potential anti-neuroinflammatory effects.
Purpose of the Study:
- To investigate the therapeutic potential of cannabigerol (CBG) in preclinical models of multiple sclerosis (MS).
- To evaluate the effects of CBG on microglial activation and inflammatory markers in vitro and in vivo.
Main Methods:
- In vitro studies using BV2 microglia and primary glial cells to assess nitric oxide and TNF-α production.
- In vivo studies using a mouse model of MS, experimental autoimmune encephalomyelitis (EAE).
- Assessment of clinical scores and histological analysis of neuronal loss in EAE mice treated with CBG.
Main Results:
- Cannabigerol (CBG) significantly reduced nitric oxide production in microglial cells.
- CBG treatment decreased inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor-α (TNF-α) levels.
- In EAE mice, CBG treatment attenuated clinical scores and restored neuronal loss.
Conclusions:
- Cannabigerol (CBG) demonstrates significant anti-neuroinflammatory and neuroprotective effects in experimental models of MS.
- CBG exhibits therapeutic potential for managing multiple sclerosis by targeting microglial activation and neurodegeneration.
