Modulation of cellular redox homeostasis by the endocannabinoid system

Lipina, Christopher; Hundal, Harinder S.

doi:10.1098/rsob.150276

Cited by 71 publications

(73 citation statements)

References 123 publications

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“…Our findings are also in agreement with those of others (reviewed in Reference ) who describe the role of the eCB system in regulating ROS production and the redox state. Whereas several studies reported that activating the eCB system confers protection from oxidative stress, others demonstrated that its stimulation results in ROS generation and cell death .…”

Section: Disscussionsupporting

confidence: 93%

Cannabinoid‐1 receptor regulates mitochondrial dynamics and function in renal proximal tubular cells

Drori

Permyakova

Hadar

et al. 2018

Diabetes Obesity Metabolism

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Section: Disscussionsupporting

confidence: 93%

Cannabinoid‐1 receptor regulates mitochondrial dynamics and function in renal proximal tubular cells

Drori

Permyakova

Hadar

et al. 2018

Diabetes Obesity Metabolism

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“…It has been shown that both AEA and 2-AG can be synthesized in the plasma membrane. However, the degradation of phosphatidylinositol by phospholipase C results in the formation of a diacylglycerol precursor, whose hydrolysis (through diacylglycerol lipase activity, DAGL) allows the formation of 2-AG [80]. However, activation of DAGLα and DAGLβ requires GSH.…”

Section: Trp Receptorsmentioning

confidence: 99%

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

2019

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Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.Antioxidants 2020, 9, 21 2 of 20 Moreover, this phytocannabinoid accelerated wound healing in a diabetic rat model by protecting the endothelial growth factor (VEGF) [11]. In addition, by preventing the formation of oxidative stress in the retina neurons of diabetic animals, CBD counteracted tyrosine nitration, which can lead to glutamate accumulation and neuronal cell death [12].This review summarizes the chemical and biological effects of CBD and its natural and synthetic derivatives. Particular attention was paid to the antioxidant and anti-inflammatory effects of CBD and its derivatives, bearing in mind the possibilities of using this phytocannabinoid to protect against oxidative stress and the consequences associated with oxidative modifications of proteins and lipids. Although CBD demonstrates safety and a good side effect profile in many clinical trials [4], all of the therapeutic options for CBD discussed in this review are limited in a concentration-dependent manner. Molecular Structure of CBDCBD is a terpenophenol compound containing twenty-one carbon atoms, with the formula C 21 H 30 O 2 and a molecular weight of 314.464 g/mol (Figure 1). The chemical structure of cannabidiol, 2-[1R-3-methyl-6R-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1, 3-benzenediol, was determined in 1963 [13]. The current IUPAC preferred terminology is 2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol. Naturally occurring CBD has a (−)-CBD structure [14]. The CBD molecule contains a cyclohexene ring (A), a phenolic ring (B) and a pentyl side chain. In addition, the terpenic ring (A) and the aromatic ring (B) are located in planes that are almost perpendicular to each other [15]. There are four known CBD side chain homologs, which are methyl, n-propyl, n-butyl, and n-pentyl [16]. All known CBD forms (Table 1) have absolute trans configuration in positions 1R and 6R [16].

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“…Importantly, these effects were prevented by a CB1 receptor antagonist [7]. Cannabinoid receptors have been shown to modulate the expression of pro-inflammatory cytokines [8]; the activation of CB1 receptors increases the level of pro-inflammatory cytokines, whereas activation of CB2 receptors promotes their reduction and generation of reactive oxygen species (ROS) [9]. Thus, endocannabinoids can simultaneously modify inflammation and oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

101

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Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte differentiation, but oxidative stress also plays an important role in the pathogenesis of this disease. Here, we examined the effect of cannabidiol (CBD), a phytocannabinoid with antioxidant and anti-inflammatory properties, on the redox balance and phospholipid metabolism in UVA/UVB-irradiated keratinocytes isolated from the skin of psoriatic patients or healthy volunteers. CBD accumulates mainly in membrane keratinocytes, especially from patients with psoriasis. This phytocannabinoid reduces the redox imbalance observed in the UV-irradiated keratinocytes of healthy subjects. It does so by decreasing reactive oxygen species (ROS) generation, increasing the Trx-dependent system efficiency, and increasing vitamin A and E levels. Consequently, a reduction in lipid peroxidation products, such as 8-isoprostanes and 4-hydroxynonenal, was also observed. Moreover, CBD modifies redox balance and lipid peroxidation in psoriatic patient keratinocytes following UV-irradiation. Interestingly, these changes are largely in the opposite direction to the case of keratinocytes from healthy subjects. CBD also regulates metabolic changes by modulating the endocannabinoid system that is disturbed by psoriasis development and UV irradiation. We observed a decrease in anandamide level in the UV-irradiated keratinocytes of healthy controls following CBD treatment, while in keratinocytes from patients treated with CBD, anandamide level was increased. However, the level of palmitoylethanolamide (PEA) was decreased in both groups treated with CBD. We further demonstrate that CBD increases CB1 receptor expression, primarily in the keratinocytes of patients, and increases CB2 receptor expression in both the psoriatic and control groups. However, CBD decreases CB2 receptor expression in UV-irradiated keratinocytes taken from patients. The UV- and psoriasis-induced activity of transmembrane transporters (Multidrug-Resistance (MDR) and breast cancer resistance protein (BCRP)) is normalized after CBD treatment. We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.

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Modulation of cellular redox homeostasis by the endocannabinoid system

Cited by 71 publications

References 123 publications

Cannabinoid‐1 receptor regulates mitochondrial dynamics and function in renal proximal tubular cells

Cannabinoid‐1 receptor regulates mitochondrial dynamics and function in renal proximal tubular cells

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

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