Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus

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.Funding: This study was entrusted by Enecta B.V. (Corantijnstraat 5-1, 1058DA Amsterdam, The Netherlands) within the project entitled "Effects of cannabidiol and cannabigerol on the neuroendocrine mechanisms underlying feeding behavior and energy balance" (Coordinators: Claudio Ferrante, Giustino Orlando and Luigi Menghini).

Biopotential of Bersama abyssinica Fresen Stem Bark Extracts: UHPLC Profiles, Antioxidant, Enzyme Inhibitory, and Antiproliferative Propensities

“…The quantitative determination of rutin and gallic was also performed through independent high-performance liquid chromatography (HPLC) coupled to fluorometric detection. The experimental conditions were selected according to our previous published paper [16]. The levels of gallic acid and rutin were expressed as mg/g dry extract.…”

“…To assess the basal cytotoxicity of B. abyssinica extract, a viability test was performed on 96 microwell plates, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Cells were incubated with extracts (0.1 mg/mL) for 24 h. An aliquot of 10 µL of MTT (5 mg/mL) was added to each well and incubated for 3 h. In the same condition, the kynurenic acid (KA) extracellular level was determined through HPLC-fluorimeter, as recently described [16].…”

“…We observed that HCT116 cell viability increased in a concentration-dependent manner, in the range 0.1-1 pg/mL, although it remained constant, at the upper tested concentrations (Figure 1). Considering that our previous ex vivo and in vitro studies focused on inflamed colon specimens and hypothalamic cells, respectively, and reported 5-HT concentrations in the order of ng/mL [16,19], we chose the 5-HT concentration 1 ng/mL as a reliable proliferative stimulus for the following tests. Specifically, the water extract was able to inhibit 5-HT-stimulated viability of HCT116 cells (Figure 2), thus, substantiating the potential antiproliferative effect of the extract in the real in vivo colon cancer cell microenvironment, characterized by the upregulated production of multiple proinflammatory and anti-apoptotic/mitogen factors, including 5-HT [24,25].…”

Evaluation of Pharmacological and Phytochemical Profiles of Piptadeniastrum africanum (Hook.f.) Brenan Stem Bark Extracts

“…Extracellular DA, NE, and 3-HK levels were analyzed by HPLC (PU-2080 chromatographic pump; Jasco, Tokyo, Japan) coupled to ESA (Chelmsford, MA, USA) Coulochem III coulometric detector, equipped with a microdialysis cell (ESA-5014b). The analytical conditions were selected according to previous studies [17,18].…”

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

“…CBG use in treating neurological diseases is, however, still unexplored [10]. In a very recent paper, the treatment of rat hypothalamus with CBD resulted in an increase in the basal 5-HT level, and a similar trend was found for CBG [11]. Nevertheless, the effect of these two compounds on brain 5-HT synthesis and release, in the framework of pro-oxidant/pro-inflammatory conditions underlying neurological disorders, needs to be better elucidated.…”