Antioxidant properties of the vasoactive endocannabinoid, 2-arachidonoyl glycerol (2-AG)

McCarron, Richard M.; Shohami, Esther; Panikashvili, David; Chen, Y.; Golech, Susanne; Strasser, Alois; Mechoulam, Raphael; Spatz, Maria

doi:10.1007/978-3-7091-0651-8_59

Cited by 10 publications

(9 citation statements)

References 16 publications

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“…The cannabis component, cannabidiol (CBD), is a potent antioxidative agent [28], and the nonpsychotropic synthetic cannabinoid, dexanabinol (HU-211), has also antioxidative properties [29]. As mentioned above, 2-AG was shown to suppress formation of ROS by murine macrophages in vitro after stimulation with lipopolysaccharide [8], and McCarron et al [30] have reported on the antioxidant properties of 2-AG.…”

Section: Head Injury: Effects Of 2-ag On Inflammatory Pathways and Oxmentioning

confidence: 93%

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Endocannabinoids and Traumatic Brain Injury

Mechoulam

Shohami

2007

Mol Neurobiol

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In response to traumatic brain injury, there is local and transient accumulation of 2-AG at the site of injury, peaking at 4 h and sustained up to at least 24 h. Neuroprotection exerted by exogenous 2-AG suggests that the formation of 2-AG may serve as a molecular regulator of pathophysiological events, attenuating the brain damage. Inhibition of this protective effect by SR-141716A, a CB(1) cannabinoid receptor antagonist, and the lack of effect of 2-AG in CB(1) knockout mice suggest that 2-AG and the CB(1) receptor may be important in the pathophysiology of traumatic brain injury. 2-AG exerts its neuroprotective effect after traumatic brain injury, at least in part, by inhibition of NF-kappaB transactivation. 2-AG also inhibits, at an early stage (2-4 h), the expression of the main proinflammatory cytokines, TNF-alpha, IL-6, and IL-1beta, and is accompanied by reduction of BBB permeability. Moreover, the CB(1), CB(2), and TRVP1 receptors are expressed on microvascular endothelial cells, and their activation by 2-AG counteracts endothelin (ET-1)-induced cerebral microvascular responses (namely, Ca(2+) mobilization and cytoskeleton rearrangement). This suggests that the functional interaction between 2-AG and ET-1 may provide a potential alternative pathway for abrogating ET-1-inducible vasoconstriction after brain injury and play a role in the neuroprotective effects exerted by 2-AG, as a potent vasodilator.

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Section: Head Injury: Effects Of 2-ag On Inflammatory Pathways and Oxmentioning

confidence: 93%

“…Antioxidants (e.g., nitroxides) have been reported to protect the BBB [37], and the findings of McCarron et al [30] provide evidence of 2-AG antioxidant activity, and thus, to its possible effects on the BBB.…”

Section: Head Injury: Effect Of 2-ag On the Blood-brain Barriermentioning

confidence: 94%

Endocannabinoids and Traumatic Brain Injury

Mechoulam

Shohami

2007

Mol Neurobiol

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“…2-AG treatment is able to reduce the permeability of the blood-brain barrier, therefore decreasing the formation of brain edema in the model of closed head injury. These effects have been attributed to the 2-AG antioxidant character [133].…”

Section: Other Disordersmentioning

confidence: 99%

Therapeutic Perspectives of Inhibitors of Endocannabinoid Degradation

Ortega-Gutiérrez

2005

CDTCNSND

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The study of the cannabinoids can be established in the middle sixties with the elucidation of the structure of the active principle of Cannabis sativa plant, the delta9-tetrahydrocannabinol. However, the existence of an endogenous cannabinoid system (ECS) has not been unequivocally accepted until recently. The last two decades have witnessed an impressive advance in the knowledge about cannabinoids, their chemistry, the enzymes involved in their metabolism, and their physiological and pathological roles. In particular, we have made progress in modifying the activity of the ECS with selective compounds, validating the ECS as a new therapeutic target. Endocannabinoids play a role in physiological and pathological processes, and their levels are affected in several disorders. Therefore, it should be possible to ameliorate these pathologies by correcting their altered levels. This review focuses on the current therapeutic opportunities of endocannabinoid-directed drugs, and pays special attention to the therapeutic possibilities underlying the inhibition of the endocannabinoid inactivation. The strategy of manipulating the ECS might open new avenues in the development of therapeutic approaches for a number of disorders, both central and peripheral, that lack as yet effective treatments.

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“…The reported TPL-induced amelioration of H 2 O 2 effects on HBEC cytoskeleton as well as Ca ?? mobilization [22,23] strengthen the concept that both actin and Ca ?? participate in vascular and microvascular function.…”

Section: Discussionmentioning

confidence: 72%

Reversal of Postischemic Hypoperfusion by Tempol: Endothelial Signal Transduction Mechanism

et al. 2011

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This report entails in vivo and in vitro studies concerned with free radical species involved in brain ischemia. The participation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the early manifestation of cerebral ischemia/reperfusion was investigated in gerbils exposed to transient global ischemia using 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL), a well-known antioxidant. TPL treatment reversed cerebral postischemic hypoperfusion and tissue edema in these animals. The findings are consistent with ROS/RNS participation in tissue injury and the reduction of cerebromicrovascular blood flow (CBF) during postischemic recirculation. The activation/deactivation of signal transduction pathway by oxidation/antioxidation [i.e., using hydrogen peroxide (H₂O₂)/TPL] was evaluated in cultured human brain endothelial cells (HBEC) to assess the involvement of endothelial-dependent mechanisms. The data showed that H₂O₂ activates various "stress" kinases and vasodilalator-stimulated phosphoprotein (VASP); activation of this pathway was reduced by inhibitors of Rho- or IP-3 kinases, as well as TPL. H₂O₂ also induced cytoskeleton (actin) rearrangements in HBEC; this effect was prevented by inhibitors of Rho/IP3 kinase or TPL. The observed activation/deactivation of H₂O₂-induced "stress" kinase is in agreement with the reported capacity of ROS/RNS to stimulate the oxidative signal transduction pathway. The noted TPL reduction of H₂O₂-induced phosphorylation of kinase strongly suggests that the beneficial effect of TPL implicates the stress signal transduction pathway. This may represent a mechanism for the cerebral postischemic manifestations observed by in vivo experiments.

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Antioxidant properties of the vasoactive endocannabinoid, 2-arachidonoyl glycerol (2-AG)

Cited by 10 publications

References 16 publications

Endocannabinoids and Traumatic Brain Injury

Endocannabinoids and Traumatic Brain Injury

Therapeutic Perspectives of Inhibitors of Endocannabinoid Degradation

Reversal of Postischemic Hypoperfusion by Tempol: Endothelial Signal Transduction Mechanism

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