Evaluation of the effects of Eserine and JWH-133 on brain dysfunction associated with experimental endotoxemia

Gamal, Maha; Moawad, Jackline; Rashed, Laila Ahmed; El‐Eraky, Wafaa I.; Saleh, Dalia O.; Lehmann, Christian; Sharawy, Nivin

doi:10.1016/j.jneuroim.2015.02.008

Cited by 13 publications

(10 citation statements)

References 59 publications

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“…In vivo , we administered a concentration of JWH-133 (1mg/kg) in line with different models of brain injuries ( Murikinati et al., 2010 ; Gamal et al., 2015 ; Fujii et al., 2016 ; Cakir et al., 2019 ). As previously described, microglia serve as the primary immune cells of the brain, releasing various pro-inflammatory cytokines ( Hanisch, 2002 ).…”

Section: Discussionmentioning

confidence: 99%

“…It has therefore been recommended as one of the most suitable CB2 agonist for preclinical target validation ( Soethoudt et al., 2017 ). It has already been shown to have beneficial effects, including downregulation of the inflammation and the improvement in neurofunctional outcome in different experimental models of brain injury, including okadaic-induced neurodegeneration ( Cakir et al., 2019 ), subarachnoid hemorrhages ( Fujii et al., 2014a ; Fujii et al., 2014b ), stroke ( Zarruk et al., 2012 ; Li et al., 2015 ; Bravo-Ferrer et al., 2017 ), endotoxemia ( Gamal et al., 2015 ), traumatic brain injury ( Amenta et al., 2014 ) or Parkinson’s disease ( Chung et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis

Pan

Grandgirard

Leib

2020

Front. Cell. Infect. Microbiol.

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Background: Microglia initiates and sustains the inflammatory reaction that drives the pathogenesis of pneumococcal meningitis. The expression of the G-protein cannabinoid receptor type 2 (CB2) in the brain is low, but is upregulated in glial cells during infection. Its activation down-regulates pro-inflammatory processes, driving microglia towards an antiinflammatory phenotype. CB2 agonists are therefore therapeutic candidates in inflammatory conditions like pneumococcal meningitis. We evaluated the effects of JWH-133, a specific CB2 agonist on microglial cells, inflammation, and damage driven by S. pneumoniae in vitro and in experimental pneumococcal meningitis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis

Pan

Grandgirard

Leib

2020

Front. Cell. Infect. Microbiol.

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“…CB2R-selective cannabinoids exert potent immunomodulatory and anti-inflammatory effects in the brain, pancreas, intestine, liver, heart, and kidney [34,35]. Activation of CB2R attenuates inflammatory states and oxidative stress in the liver [75][76][77], lungs [50], heart [39], kidney [87], intestine [93], brain [135], and in sepsis [78] by inhibiting inflammatory cell recruitment, proinflammatory cytokines, and increasing levels of anti-inflammatory cytokines.…”

Section: Cb2 Receptors Mediated Protective Effects Of Jwh133 In Organ Injuries and Sepsismentioning

confidence: 99%

“…Acute central nervous system (CNS) injury perturbs the homeostasis of the CNS and immune system and enhances patient susceptibility to infections [136]. JWH133 shows neuroprotective effects in LPS-induced neuroinflammation and endotoxemia by mitigating levels of proinflammatory cytokines, adhesion molecules (vascular cell adhesion protein 1 and E-selectin), and oxidative/nitrosative stress [135]. Based on the role of JWH133 in ameliorating sepsis, JWH133 appears to be a potent candidate for limiting COVID-19 progression and post-infection sequelae, including its impact on the multi-organ system.…”

Section: Cb2 Receptors Mediated Protective Effects Of Jwh133 In Organ Injuries and Sepsismentioning

confidence: 99%

Cannabinoid Type-2 Receptor Agonist, JWH133 May Be a Possible Candidate for Targeting Infection, Inflammation, and Immunity in COVID-19

Jha

Sharma

Meeran

et al. 2021

Immuno

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The COVID-19 pandemic, caused by SARS-CoV-2, is a deadly disease affecting millions due to the non-availability of drugs and vaccines. The majority of COVID-19 drugs have been repurposed based on antiviral, immunomodulatory, and antibiotic potential. The pathogenesis and advanced complications with infection involve the immune-inflammatory cascade. Therefore, a therapeutic strategy could reduce infectivity, inflammation, and immune modulation. In recent years, modulating the endocannabinoid system, particularly activation of the cannabinoid type 2 (CB2) receptor is a promising therapeutic target for modulation of immune-inflammatory responses. JWH133, a selective, full functional agonist of the CB2 receptor, has been extensively studied for its potent anti-inflammatory, antiviral, and immunomodulatory properties. JWH133 modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. In this study, we propose that JWH133 could be a promising candidate for targeting infection, immunity, and inflammation in COVID-19, due to its pharmacological and molecular mechanisms in numerous preclinical efficacy and safety studies, along with its immunomodulatory, anti-inflammatory, organoprotective, and antiviral properties. Thus, JWH133 should be investigated in preclinical and clinical studies for its potential as an agent or adjuvant with other agents for its effect on viremia, infectivity, immune modulation, resolution of inflammation, reduction in severity, and progression of complications in COVID-19. JWH133 is devoid of psychotropic effects due to CB2 receptor selectivity, has negligible toxicity, good bioavailability and druggable properties, including pharmacokinetic and physicochemical effects. We believe that JWH133 could be a promising drug and may inspire further studies for an evidence-based approach against COVID-19.

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“…Systemic inflammation due to aging or disease states (such as obesity, cardiovascular disease, sepsis and infection) can directly impact functioning within the brain. (Batista et al, 2019;Gamal et al, 2015Gamal et al, , 2018Srinivasan & Lahiri, 2015;Walker, 2019).…”

Section: Introductionmentioning

confidence: 99%

IκB kinase inhibition remodeled connexins, pannexin‐1, and excitatory amino‐acid transporters expressions to promote neuroprotection of galantamine and morphine

Magdy

Gamal

Samir

et al. 2021

Journal Cellular Physiology

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Inflammatory pathway and disruption in glutamate homeostasis join at the level of the glia, resulting in various neurological disorders. In vitro studies have provided evidence that membrane proteins connexions (Cxs) are involved in glutamate release, meanwhile, excitatory amino-acid transporters (EAATs) are crucial for glutamate reuptake (clearance). Moreover, pannexin-1 (Panx-1) activation is more detrimental to neurons. Their expression patterns during inflammation and the impacts of IκB kinase (IKK) inhibition, morphine, and galantamine on the inflammatory-associated glutamate imbalance remain elusive.To investigate this, rats were injected with saline or lipopolysaccharide.Thereafter, vehicles, morphine, galantamine, and BAY-117082 were administered in different groups of animals. Subsequently, electroencephalography, enzyme-linked immunosorbent assay, western blot, and histopathological examinations were carried out and various indicators of inflammation and glutamate level were determined. Parallel analysis of Cxs, Panx-1, and EAAts in the brain was performed. Our findings strengthen the concept that unregulated expressions of Cxs, Panx-1, and EAATs contribute to glutamate accumulation and neuronal cell loss. Nuclear factor-kB (NF-κB) pathway can significantly contribute to glutamate homeostasis via modulating Cxs, Panx-1, and EAATs expressions. BAY-117082, via inhibition of IkK, promoted the antiinflammatory effects of morphine as well as galantamine. We concluded that NF-κB is an important component of reshaping the expressions of Cxs, panx-1, and EAATs and the development of glutamate-induced neuronal degeneration.

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Evaluation of the effects of Eserine and JWH-133 on brain dysfunction associated with experimental endotoxemia

Cited by 13 publications

References 59 publications

Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis

Adjuvant Cannabinoid Receptor Type 2 Agonist Modulates the Polarization of Microglia Towards a Non-Inflammatory Phenotype in Experimental Pneumococcal Meningitis

Cannabinoid Type-2 Receptor Agonist, JWH133 May Be a Possible Candidate for Targeting Infection, Inflammation, and Immunity in COVID-19

IκB kinase inhibition remodeled connexins, pannexin‐1, and excitatory amino‐acid transporters expressions to promote neuroprotection of galantamine and morphine

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