The beneficial properties of CBDA in diet-induced neuroinflammation.

Cannabidiolic acid (CBDA) is a phytocannabinoid found in the Cannabis plant. Understanding the effects of CBDA is essential to uncover its full potential and possible health benefits. The study was conducted on rats receiving standard rat chow (control) and a high-fat diet (HFD). Half of the animals in each group were administered CBDA intragastrically. The total lipid fractions and arachidonic acid (AA) contents were measured in the frontal and posterior cortex, hippocampus, and subcortical nuclei using gas-liquid chromatography. The expression of proteins involved in neurodegenerative diseases and insulin signaling pathway proteins in the frontal and posterior cortex was measured using Immunoblotting. RT-PCR was used to assess the expression of pro-inflammatory pathway proteins in the same regions. Additionally, untargeted and targeted metabolomic analyses were performed on cerebrospinal fluid (CSF). The results showed that a decrease in arachidonic acid levels and pro-inflammatory precursor proteins after CBDA treatment in high-fat-fed rats was simultaneous with improved insulin signaling, particularly in the posterior cortex. Inactivation of glycogen synthase kinase 3 (GSK-3β) in this region was concomitant with changes in neurodegenerative biomarkers in the cortex and CSF. Metabolomic studies revealed a significant diminishment in creatinine, phenylalanine, and sarcosine levels in the HFD+CBDA group, suggesting it plays an important role in neurological disorders. The results suggest that CBDA has anti-inflammatory properties by reducing the synthesis of lipid inflammatory mediators, which are concomitant with improved insulin signaling and probably reduced neurodegeneration. Thus, CBDA could be considered as a part of future clinical treatment for many inflammatory conditions.