The cannabinoid dexanabinol is an inhibitor of the nuclear factor-kappa B (NF-κB)

Jüttler, Eric; Potrovita, Ioana; Tarabin, Victoria; Prinz, Simone; Dong‐Si, Tuan; Fink, George; Schwaninger, Markus

doi:10.1016/j.neuropharm.2004.05.009

Cited by 49 publications

(29 citation statements)

References 54 publications

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“…Because these non-psychoactive enantiomers have a different configuration, they may not be able to bind the cannabinoid receptors as well as the psychoactive compounds. For example, HU-211 (dexanabinol), a synthetic analog of tetrahydrocannabinol, does not bind CB1 or CB2 [36]. Consequently, such enantiomers may not be able to induce apoptosis in lymphocytes and prevent their proliferation.…”

Section: Discussionmentioning

confidence: 99%

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

Lombard

Nagarkatti

2007

Clinical Immunology

103

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Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2 selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents.

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Section: Discussionmentioning

confidence: 99%

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

Lombard

Nagarkatti

2007

Clinical Immunology

103

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“…megestrol acetate, Dronabinol, Eicosapentaenoic acid-enriched oral supplements, Ghrelin, Pentoxiphylline, thalidomide, melatonin, nandrolone decanoate) have been identified which were effective in treatment of cachexia/ anorexia to some extent in randomized clinical trails in cancer patients. Although the mechanisms of action of these drugs in prevention of cachexia in cancer patients remain to be determined, many of these drugs such as Dexanabinol [70], Eicosapentaenoic acid [71], Ghrelin [72], Pentoxiphylline [73], thalidomide [74], and melatonin [75] have been shown to inhibit NF-κB activity in different cell types.…”

Section: Cancermentioning

confidence: 99%

Nuclear factor-kappa B signaling in skeletal muscle atrophy

2008

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Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-κB) is one of most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-κB in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-κB can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-κB in skeletal muscle with particular reference to different models of muscle-wasting and the development of novel therapy.

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“…Recent studies also indicate that acetylsalicylic acid inhibits tau phosphorylation [127] . Other potentially interesting anti-inflammatory drugs have also been reported to exert neuroprotective effects and inhibit NF-κB, including cannabinoid dexanabinol and caffeic acid [128][129][130] . Recent studies have identified that cyclopentenone prostaglandins (cPG), including prostaglandin (PG)A1 and PGJ2 are ligands for peroxisome-proliferation activator receptor-γ and inhibitors of NF-κB.…”

Section: Nf-κb Inhibitors and Neuroprotective Therapymentioning

confidence: 99%

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

Qin

Tao

Chen

2007

Acta Pharmacologica Sinica

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NF-κB is a well-characterized transcription factor with multiple physiological and pathological functions. NF-κB plays important roles in the development and maturation of lymphoids, regulation of immune and inflammatory response, and cell death and survival. The influence of NF-κB on cell survival could be protective or destructive, depending on types, developmental stages of cells, and pathological conditions. The complexity of NF-κB in cell death and survival derives from its multiple roles in regulating the expression of a broad array of genes involved in promoting cell death and survival. The activation of NF-κB has been found in many neurological disorders, but its actual roles in pathogenesis are still being debated. Many compounds with neuroprotective actions are strongly associated with the inhibition of NF-κB, leading to speculation that blocking the pathological activation of NF-κB could offer neuroprotective effects in certain neurodegenerative conditions. This paper reviews the recent developments in understanding the dual roles of NF-κB in cell death and survival and explores its possible usefulness in treating neurological diseases. This paper will summarize the genes regulated by NF-κB that are involved in cell death and survival to elucidate why NF-κB promotes cell survival in some conditions while facilitating cell death in other conditions. This paper will also focus on the effects of various NF-κB inhibitors on neuroprotection in certain pathological conditions to speculate if NF-κB is a potential target for neuroprotective therapy.

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The cannabinoid dexanabinol is an inhibitor of the nuclear factor-kappa B (NF-κB)

Cited by 49 publications

References 54 publications

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents

Nuclear factor-kappa B signaling in skeletal muscle atrophy

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

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