Effect of Cannabidiol in LPS-induced toxicity in astrocytes: Possible role for cannabinoid type-1 receptors

Autor: Hind IBORK, Sara EL IDRISSI, Simo SIYANDA Zulu, Robert MILLER, Lhoussain HAJJI, Annabelle MANALO MORGAN, Khalid TAGHZOUTI, Oualid ABBOUSSI
Rok vydání: 2023
Popis: Cerebral metabolic abnormalities are common in neurodegenerative diseases. Previous studies have shown that mitochondrial damage alters ATP production and increases Reactive Oxygen Species (ROS) release which may contribute to neurodegeneration. In the present study, we investigated the neuroprotective effects of cannabidiol (CBD), a non-psychoactive component derived from marijuana (Cannabis sativa L.), on astrocytic bioenergetic balance; in a primary cell culture model of lipopolysaccharide (LPS)-induced neurotoxicity. Astrocytic metabolic profiling using an extracellular flux analyzer demonstrated that CBD decreases mitochondrial proton leak, increased spare respiratory capacity and coupling efficiency in LPS-stimulated astrocytes. Simultaneously CBD increased astrocytic glycolytic capacity and glycolysis reserve in a cannabinoid receptor type 1 (CB1) dependent manner. CBD-restored metabolic changes were correlated with a significant decrease in the pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) concentration, and a reduction of ROS production in LPS-stimulated astrocytes. These results suggest that CBD may inhibit LPS-induced metabolic impairments and inflammation by enhancing astrocytic metabolic glycolysis versus oxidative phosphorylation through its action on CB1 receptors. The present findings suggest CBD as a potential anti-inflammatory treatment in metabolic pathologies and highlight a possible role for the cannabinoidergic system in the modulation of mitochondrial oxidative stress.
Databáze: OpenAIRE