Ajulemic acid, a synthetic cannabinoid acid, induces an antiinflammatory profile of eicosanoids in human synovial cells

Stebulis, Judith A.; Johnson, David R.; Rossetti, Ronald G.; Zurier, Robert B.

doi:10.1016/j.lfs.2008.09.004

Cited by 32 publications

(32 citation statements)

References 49 publications

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“…This upregulation has been also demonstrated after the administration of ajulemic acid to human synovial cells (Stebulis et al, 2008), inducing an antiinflammatory profile of eicosanoids. PPARg regulation is not yet completely understood, but one of the main mechanisms may be ligand availability (Daynes and Jones, 2002).…”

Section: Discussionmentioning

confidence: 67%

Regulatory Role of Cannabinoid Receptor 1 in Stress-Induced Excitotoxicity and Neuroinflammation

Zoppi

Nievas

Madrigal

et al. 2010

Neuropsychopharmacol

103

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Exposure to stress elicits excitoxicity and neuroinflammation in the brain, contributing to cell death and damage in stress-related neurological and neuropsychiatric diseases. The endocannabinoid system is present in stress-responsive neural circuits and has been proposed as an endogenous neuroprotective system activated in some neuropathological scenarios to restore homeostasis. To elucidate the possible regulatory role of cannabinoid receptor 1 (CB1) in stress-induced excitotoxicity and neuroinflammation, both genetic and pharmacological approaches were used alternatively: (1) wild-type (WT) and CB1 knockout mice (CB1-KO) were exposed to immobilization/acoustic stress (2 h/day for 4 days) and (2) to specifically activate CB1, the selective CB1 agonist Arachidonyl-2'-chloroethylamide (ACEA) (2.5 mg/kg) was intraperitoneally administered daily to some groups of animals. Stress exposure increased CB1 mRNA and protein expression in the prefrontal cortex of WT mice in a mechanism related to N-methyl-D-aspartate glutamate receptor activation. Daily ACEA pretreatment prevented stress-induced: (1) upregulation of CB1 mRNA and protein, (2) decrease in glutamate uptake and glutamate astroglial transporter excitatory amino acid transporter 2 expression, (3) increase in consecutive proinflammatory molecules, such as cytokines (tumor necrosis factor-α and MCP-1), nuclear factor kappa B, and enzymatic sources, such as inducible nitric oxide synthase (NOS-2) and cyclooxygenase-2 (COX-2), (4) increase in lipid peroxidation; although having no effect on plasma corticosterone. Interestingly, a possible related mechanism could be the positive ACEA modulation of the antiinflammatory pathway deoxyprostaglandin/peroxisome proliferator-activated receptor γ (15d-PGJ(2)/PPARγ). Conversely, KO animal experiments indicated that a lack of CB1 produces hypothalamic/pituitary/adrenal (HPA) axis dysregulation and exacerbates stress-induced excitotoxic/neuroinflammatory responses. These multifaceted neuroprotective effects suggest that CB1 activation could be a new therapeutic strategy against neurological/neuropsychiatric pathologies with HPA axis dysregulation and an excitotoxic/neuroinflammatory component in their pathophysiology.

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Section: Discussionmentioning

confidence: 67%

Regulatory Role of Cannabinoid Receptor 1 in Stress-Induced Excitotoxicity and Neuroinflammation

Zoppi

Nievas

Madrigal

et al. 2010

Neuropsychopharmacol

103

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“…By way of comparison, the anti inflammatory actions of cannabinoid analogs such as NAgly 24 and ajulemic acid ( Fig. 2) 25 have been attributed to their ability to promote the release of free arachidonic acid.…”

Section: Arachidonic Acid Releasementioning

confidence: 99%

Cannabidiol (CBD) and its analogs: a review of their effects on inflammation

Burstein

2015

Bioorganic & Medicinal Chemistry

476

332

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“…Ajulemic acid reduced production of the inflammatory mediators interleukin-1β and interleukin-6, induced T cell apoptosis, and increased anti-inflammatory eicosanoids prostaglandin J2 and lipoxin A4 (Bidinger et al, 2003, Parker et al, 2008, Stebulis et al, 2008, Zurier et al, 2003, Zurier et al, 2009). Furthermore, multiple clinical trials of ajulemic acid administered orally found no serious adverse effects and no marijuana-like neurological effects (Corbus Pharmaceuticals’ clinical investigator brochure for JBT-101, version 1.11).…”

Section: To the Editormentioning

confidence: 99%

Cannabinoid Reduces Inflammatory Cytokines, Tumor Necrosis Factor-α, and Type I Interferons in Dermatomyositis In Vitro

Robinson

Alves

Bashir

et al. 2017

Journal of Investigative Dermatology

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Ajulemic acid, a synthetic cannabinoid acid, induces an antiinflammatory profile of eicosanoids in human synovial cells

Cited by 32 publications

References 49 publications

Regulatory Role of Cannabinoid Receptor 1 in Stress-Induced Excitotoxicity and Neuroinflammation

Regulatory Role of Cannabinoid Receptor 1 in Stress-Induced Excitotoxicity and Neuroinflammation

Cannabidiol (CBD) and its analogs: a review of their effects on inflammation

Cannabinoid Reduces Inflammatory Cytokines, Tumor Necrosis Factor-α, and Type I Interferons in Dermatomyositis In Vitro

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