Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues

Gallelli, Cristina Anna; Calcagnini, Silvio; Romano, Adele; Koczwara, Justyna Barbara; Ceglia, Marialuisa de; Dante, Donatella; Villani, Rosanna; Giudetti, Anna Maria; Cassano, Tommaso; Gaetani, Silvana

doi:10.3390/antiox7070093

Cited by 82 publications

(79 citation statements)

References 417 publications

(556 reference statements)

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“…CBD has recently been shown to modulate the endocannabinoid system activity by increasing anandamide (AEA) levels [5], which can affect cannabinoids signaling, including their interaction on cannabinoid receptors [57]. However, it is known that the peroxisome proliferator-activated receptor alpha (PPAR-α), for example, activated by endocannabinoids, directly regulates the expression of antioxidant enzymes such as superoxide dismutase by interacting with their promoter regions [58]. Therefore, it is believed that the most important antioxidant activity of CBD, like endocannabinoids, is associated with its effect on receptors.…”

Section: Indirect Antioxidant Effects Of Cbdmentioning

confidence: 99%

“…CBD antagonism is manifested as an anticonvulsant effect [96]. Because CBD increases endocannabinoid expression, it can also indirectly affect inflammation and redox balance via these molecules [58]. In addition, GPR55 knockout mice have been shown to have high levels of anti-inflammatory interleukins (IL-4, IL-10, and IFN-γ) [97], while high expression of GPR55 reduces ROS production [98].…”

Section: Gpr Receptorsmentioning

confidence: 99%

“…It causes vasodilation independent of the receptors as well [2,127]. Therefore, it has been suggested that O-1602 can be used to regulate ROS/RNS levels and modify the effect of oxidative stress on cellular metabolism by modulating GPR55 receptor activation [58]. In addition, O-1602, as a GPR18 agonist, mediates the reduction of cyclic adenosine monophosphate (cAMP) and the activation of the PI3K/AKT and ERK1/2 pathways in vitro [128].…”

Section: Gpr Receptorsmentioning

confidence: 99%

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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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Section: Indirect Antioxidant Effects Of Cbdmentioning

confidence: 99%

Section: Gpr Receptorsmentioning

confidence: 99%

Section: Gpr Receptorsmentioning

confidence: 99%

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Antioxidative and Anti-Inflammatory Properties of Cannabidiol

2019

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“…Antioxidant enzymes can be modulated by eCBs, not only acting on the CB1 and CB2 receptors, but also through the transient receptor potential vanilloid-1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPAR-alpha), and the orphan receptors Narachidonyl glycine receptor or G-protein-coupled receptors 18 (GPR18) GPR19 and GPR55 (Piomelli, 2003;McHugh et al, 2010;Howlett et al, 2011;McHugh, 2012). Therefore, the direct and/or indirect modulation of pathways through which the eCBs damper the OS may represent a promising strategy for reducing the damage caused by a redox imbalance (Gallelli et al, 2018). Moreover, antioxidants are now seen as a convincing therapy against severe neurodegeneration, as they have the ability to fight it by blocking the OS.…”

Section: Introductionmentioning

confidence: 99%

From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases

et al. 2020

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Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects. Besides D9-tetrahydrocannabinol that is the principal psychoactive constituent of Cannabis, cannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for antiinflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression. To this regard, Alzheimer's disease (AD), Parkinson's disease (PD), the most common neurodegenerative disorders, are characterized by extensive oxidative damage to different biological substrates that can cause cell death by different pathways. Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes; therefore, promising treatment strategies should simultaneously target multiple substrates in order to stop and/ or slow down the neurodegeneration. In this context, CBD, which interacts with the eCB system, but has also cannabinoid receptor-independent mechanism, might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders, such as PD and AD. This review summarizes the multiple molecular pathways that underlie the positive effects of CBD, which may have a considerable impact on the progression of the major neurodegenerative disorders.

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“…Accession of PPAR can both decrease and increase the intensity of transcription of the corresponding genes. The identification of PPRE in the promoter regions of the catalase and superoxide dismutase genes indicates the involvement of these nuclear receptors in reducing the production of ROS and lipid peroxidation (LPO) products [9].…”

mentioning

confidence: 99%

Free radical oxidation in liver mitochondria of tumor-bearing rats and its correction by essential lipophilic nutrients

Ketsa¹,

Марченко²

2020

Ukr.Biochem.J

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the role of free radical oxidation in the increase of mitochondrial membranes permeability in organs which are not involved in oncogenesis and the development of the methods for preventing mitochondria dysfunction remain topical problems. In this work, the interconnection of lipid peroxidation (LPO) in liver mitochondrial fraction with the processes of mitochondrial swelling and cytochrome с release to the cytosol under separate and combined administration of ω-3 polyunsaturated fatty acids (PUFAs) and retinol acetate (vitamin a acetate) to rats with transplanted Guerin's carcinoma was studied. During the intensive tumor growth (14 days) the increase of superoxide radical generation and the content of primary (triene conjugates, tc), secondary (ketodienes and coupled trienes, CD+CT) and terminal (Schiff bases) lipid peroxidation products in the mitochondrial fraction of tumor-bearing rats was detected, which contributed to the mitochondrial swelling and cytochrome с release to the cytosol. Separate administration of ω-3 PUFAs to tumor-bearing rats decreased both free radical processes in mitochondrial fraction and mitochondrial swelling. Separate administration of retinol acetate in a high dose (3000 IU/kg of body weight) intensified free radical processes in the mitochondrial fraction of tumor-bearing rats, while administration of retinol acetate in a physiological dose (30 IU/kg of body weight) did not lead to changes compared to tumor-bearing rats that did not receive the drug. The prooxidant effects of retinoid were partially eliminated in the case of combined administration with ω-3 PUFA. K e y w o r d s: liver mitochondrial fraction, lipid peroxidation, cytochrome c, mitochondrial swelling, ω-3 polyunsaturated fatty acids, retinol acetate, Guerin's carcinoma.

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Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues

Cited by 82 publications

References 417 publications

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases

Free radical oxidation in liver mitochondria of tumor-bearing rats and its correction by essential lipophilic nutrients

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