Abstract
Background: Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite although there are no studies elucidating their role in the hypothalamic appetite-regulating network. Consequently, the aim of the present research is to investigate the role of CBD and CBG in regulating hypothalamic neuromodulators. Comparative evaluations between oxidative stress and food intake-modulating mediators were also performed. Methods: Rat hypothalamic Hypo-E22 cells and isolated tissues were exposed to either CBD or CBG, and the gene expressions of neuropeptide (NP)Y, pro-opiomelanocortin (POMC) and fatty acid amide hydrolase were assessed. In parallel, the influence of CBD on the synthesis and release of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) was evaluated. The 3-hydroxykinurenine/kinurenic acid (3-HK/KA) ratio was also determined. Results: Both CBD and CBG inhibited NPY and POMC gene expression and decreased the 3-HK/KA ratio in the hypothalamus. The same compounds also reduced hypothalamic NE synthesis and DA release, whereas the sole CBD inhibited 5-HT synthesis. Conclusion: The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways.
Highlights
Cannabis sativa has long been considered as an efficacious pharmacological tool to treat a wide plethora of diseases, including fever, malaria, constipation, menstrual disorders, pain, and rheumatism.The plant, belonging to the Cannabaceae family and classified in the three recognized varieties, is characterized by the presence of numerous terpenophenolic compounds that are responsible, at least partially, for the aforementioned effects
The endocannabinoid-mediated activation of cannabinoid type 1 (CB1) and CB2 has long been implicated in the onset of neuroprotective effects, whereas the neuroprotection occurring after phyto-cannabinoid administration could be better explained by a multitarget mechanism involving different receptor systems, including peroxisome proliferator-activated receptors (PPARs) and transient receptor potential (TRP) channels [3,4,5]
The CBD could represent an innovative pharmacological approach: even though it is described as a CB1 ligand, the CBD was reported to have a low affinity for the CB1 orthosteric site [9], and this could be considered as one of the main factors influencing the lack of psychiatric symptoms following the administration in vivo [10]
Summary
Cannabis sativa has long been considered as an efficacious pharmacological tool to treat a wide plethora of diseases, including fever, malaria, constipation, menstrual disorders, pain, and rheumatism.The plant, belonging to the Cannabaceae family and classified in the three recognized varieties (sativa, indica and ruderalis), is characterized by the presence of numerous terpenophenolic compounds that are responsible, at least partially, for the aforementioned effects. The therapeutic failure was ascribed, at least partially, to the specific mechanism of action of the drug, whose orthosteric inverse agonism on CB1 could lead to supra-physiological receptor alterations [8] To this regard, the CBD could represent an innovative pharmacological approach: even though it is described as a CB1 ligand, the CBD was reported to have a low affinity for the CB1 orthosteric site [9], and this could be considered as one of the main factors influencing the lack of psychiatric symptoms following the administration in vivo [10]. Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite there are no studies elucidating their role in the hypothalamic appetite-regulating network. Conclusion: The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways
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