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Research Library

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Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells

  • Journal : Journal of Basic and Clinical Physiology and Pharmacology
  • Publication Year : 2016
  • Authors : Ana Juknat; Ewa Kozela; Nathali Kaushansky; Raphael Mechoulam; Zvi Vogel

Background: Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be antiinflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells.
Methods: BV-2 cells were pretreated with DMH-CBD, followed by stimulation with the endotoxin lipopolysaccharide (LPS). The expression levels of selected genes involved in stress regulation and inflammation were determined by
quantitative real-time PCR. In addition, MOG35–55-reactive T cells (TMOG) were cultured with antigen-presenting cells in the presence of DMH-CBD and MOG35–55 peptide, and cell proliferation was determined by measuring [3
H]thymidine incorporation.
Results: DMH-CBD treatment downregulated in a dose-dependent manner the mRNA expression of LPS-upregulated pro-inflammatory genes (Il1b, Il6, and Tnf) in BV-2 microglial cells. The expression of these genes
was also downregulated by DMH-CBD in unstimulated cells. In parallel, DMH-CBD upregulated the expression of
genes related to oxidative stress and glutathione homeostasis such as Trb3, Slc7a11/xCT, Hmox1, Atf4, Chop,
and p8 in both stimulated and unstimulated microglial cells. In addition, DMH-CBD dose-dependently inhibited
MOG35–55-induced TMOG proliferation.
Conclusions: The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD. DMH-CBD
downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive
cellular response against inflammatory stimuli and oxidative injury. In addition, DMH-CBD decreases the proliferation of pathogenic activated TMOG cells.

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Conditions:

  • Inflammation, MTHFR Gene Mutation

Research Information:

Research Keywords:

  • anti-inflammation, cannabidiol, Cannabinoids, cystine/glutamate transporter, dimethylheptyl-cannabidiol, gene expression, glutathione, Microglia, oxidative stress, proliferation, T cells

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