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cbd oil antioxidant

Cbd oil antioxidant

CB1 and CB2 are receptors with strong expression in the central nervous system and the immune system primarily, but also occur in other tissues. CBD, acting on the above receptors, inhibits the activity of adenylyl cyclase and voltage gated calcium channels, activates potassium channels and activates mitogen activated protein kinase (MAPK), 3-phosphoinositol kinase (PI3K)/AKT, and the mammalian target of rapamycin (mTOR) signaling pathways [68]. The PI3K/AKT/mTOR pathway is one of the basic pathways necessary for physiological protein synthesis and induction of other intracellular pathways, such as the MAPK pathway, which plays an important role in regulating cell survival, proliferation, and apoptosis [69]. CBD was found to induce apoptosis in leukemia cells by reducing p38-MAPK levels [70]. However, CBD was also shown to inhibit apoptosis in human breast cancer cell lines (T-47D and MDA-MB-231) by inhibiting expression of oncogenic and pro-survival cyclin D1 and mTOR, and by increasing PPARγ receptor expression [71].

PPARγ cooperates also with another transcription factor, Nrf2, which controls the expression of genes encoding cytoprotective proteins, particularly antioxidant proteins [28,88]. PPARγ may bind to specific elements in the promoter region of genes it regulates, including Nrf2, catalase (CAT), glutathione S-transferase (GST), heme-oxygenase-1 (HO-1), and manganese-dependent superoxide dismutase (Mn-SOD). In contrast, Nrf2 can regulate PPARγ expression by binding to the PPARγ promoter in the sequence of antioxidant response elements (ARE) that are located in the -784/-764 and -916 regions of the PPARγ promoter [89,90]. The reduction in PPARγ expression in Nrf2 knockout mice provides confirmation of this regulation [91].

3.7. GPR Receptors

Given the limitations in the biological activity of CBD itself and its natural derivatives and the fact that the biological properties of CBD derivatives depend on their structure, synthetic derivatives are produced that have been designed so that their structure allows direct interaction with components of the redox system or indirectly with molecular targets interacting with these components, including the cannabinoid receptors ( Table 2 ). The derivatives with potential antioxidant and anti-inflammatory effects include, but are not limited to, (+)-CBD derivatives, dihydrocannabidiol and tetrahydrocannabidiol derivatives, and (+)-dihydro-7-hydroxy-CBD [2]. Promising synthetic derivatives that can modulate redox balance and/or inflammation are presented below.

CBD has a wide spectrum of biological activity, including antioxidant and anti-inflammatory activity, which is why its activity in the prevention and treatment of diseases whose development is associated with redox imbalance and inflammation has been tested [4,19,20]. Based on the current research results, the possibility of using CBD for the treatment of diabetes, diabetes-related cardiomyopathy, cardiovascular diseases (including stroke, arrhythmia, atherosclerosis, and hypertension), cancer, arthritis, anxiety, psychosis, epilepsy, neurodegenerative disease (i.e., Alzheimer’s) and skin disease is being considered [20,21,22]. Analysis of CBD antioxidant activity showed that it can regulate the state of redox directly by affecting the components of the redox system and indirectly by interacting with other molecular targets associated with redox system components.

3.9. Adenosine A2A Receptors

Influence of natural and synthetic CBD derivatives on receptor activation (X: agonist activation or Y: antagonist activation by related CBD derivative; * weak affinity; #: full name is in chapter 4.1) [2,24,72,76,114,115,116,120,122,123,124,125,126,127,130].

The involvement of calcium and calcium channels in AMPA/kainate-mediated toxicity. The effects of 2 mM EDTA and various combinations of the voltage-sensitive calcium channel inhibitors ω-Agatoxin IVa (Ag) (250 nM), ω-Conotoxin GVIa (CTx) (500 nM), and Nifedipine (Nif) (1 μM) were used to probe the role and source of calcium in AMPA/kainate receptor-mediated toxicity. Data represents mean values ± SEM from four experiments, each with four replicates. Cannabinoids were present throughout the glutamate exposure period. See Materials and Methods for further experimental details. Significant difference between EDTA and other treatments is indicated with an asterisk.

Effect of cannabidiol on NMDAr- (A) and AMPA/kainate receptor- (B) mediated neurotoxicity. Data shown represents mean values ± SEM from a single experiment with four replicates. Each experiment was repeated on at least four occasions with essentially the same results. Cannabinoids were present during (and, in the case of NMDAr mediated toxicity, after) the glutamate exposure periods. See Materials and Methods for further experimental details.

Cyclic voltametry was performed with an EG & G Princeton Applied Research potentiostat/galvanostat ( model 273/ par 270 software). The working electrode was a glassy carbon disk with a platinum counter electrode and silver/silver chloride reference. Tetraethylammonium chloride in acetonitrile (0.1 M) was used as an electrolyte. Cyclic voltametry scans were done from 0 to +1.8 V at scan rate of 100 mV per second.

Data Analysis.

(A) A comparison of the oxidation potentials of cannabinoids and the antioxidant BHT. The oxidation profiles of (750 μM) BHT, cannabinoids, and anandamide were compared by cyclic voltametry. Anandamide, a cannabinoid receptor ligand with a noncannabinoid structure, was used as a nonresponsive control. Experiments were repeated three times with essentially the same results. See Materials and Methods for experimental details. (B) Effect of cannabidiol and THC on dihydrorhodamine oxidation. Cannabinoids were compared with BHT for their ability to prevent tert-butyl hydroperoxide-induced oxidation of dihydrorhodamine. See Materials and Methods for experimental details. Data represent mean values ± SEM from a single experiment with three replicates. This experiment was repeated four times with essentially the same results.

Effect of THC, cannabidiol, and cannabinoid receptor antagonist on glutamate induced neurotoxicity. Neurons exposed to glutamate in an AMPA/kainate receptor toxicity model were incubated with 10 μM cannabidiol or THC in the presence or absence of SR141716A (500nM). See Materials and Methods for experimental details. Data represents mean values ± SEM from four experiments, each with three replicates.

Cyclic Voltametry.

Solutions of cannabinoids, cyclothiazide, and other lipophiles were prepared by evaporating a 10 mM ethanolic solution (under a stream of nitrogen) in a siliconized microcentrifuge tube. Dimethyl sulfoxide (<0.05% of final volume) was added to ethanol to prevent the lipophile from completely drying onto the tube wall. After evaporation, 1 ml of culture media was added, and the drug was dispersed by using a high power sonic probe. Special attention was used to ensure the solution did not overheat or generate foam. After dispersal, all solutions were made to their final volume in siliconized glass tubes by mixing with an appropriate quantity of culture media.

Astrocyte-conditioned DMEM (phenol red-free) was used throughout the AMPA/kainate toxicity procedure and after glutamate exposure in the NMDAr-mediated toxicity protocol. Media were conditioned by 24 hr of treatment over a confluent layer of type I astrocytes prepared from 2-day-old Wistar rat pups (14). In brief, cortices were dissected, were cut into small pieces, were digested enzymatically with 0.25% trypsin, and then were dissociated mechanically by passage through a plastic pipette. The cell suspension then was plated into untreated 75-cm 2 T-flasks, and, after 24 hr, the media were replaced and unattached cells were removed. Once astrocytes achieved confluency, cells were divided into four flasks. Media for experiments were conditioned by a 24-hr exposure to these astrocytes, after which time they were frozen at −20°C until use. Astrocyte cultures were used to condition DMEM for no longer than 2 months.