Cannabinoid-based drugs as anti-inflammatory therapeutics

Klein, Thomas

doi:10.1038/nri1602

Cited by 642 publications

(551 citation statements)

References 114 publications

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“…29,42 The present results corroborate these data by showing a great increase of CB2 mRNA expression in colonic tissue from DSS-treated mice, compared with colons from the control group ( Figure 6E). Of note, preventive oral treatment with BCP markedly diminished CB2 expression in colons from mice on day 7 after DSS treatment ( Figure 6E).…”

Section: Beneficial Effects Of ␤-Caryophyllene On Dss-induced Colitissupporting

confidence: 88%

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

Bento

Marcon

Dutra

et al. 2011

The American Journal of Pathology

212

145

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Cannabinoid receptor 2 (CB2) activation is suggested to trigger the peroxisome proliferator-activated receptor-␥ (PPAR␥) pathway, and agonists of both receptors improve colitis. Recently, the plant metabolite (E)-␤-caryophyllene (BCP) was shown to bind to and activate CB2. In this study, we examined the antiinflammatory effect of BCP in dextran sulfate sodium (DSS)-induced colitis and analyzed whether this effect was mediated by CB2 and PPAR␥. Oral treatment with BCP reduced disease activity, colonic macro-and microscopic damage, myeloperoxidase and N-acetylglucosaminidase activities, and levels and mRNA expression of colonic tumor necrosis factor-␣, IL-1␤, interferon-␥, and keratinocyte-derived chemokine. Inflammatory bowel diseases (IBDs) are a group of chronic diseases that affect the gastrointestinal tract and have been mainly subdivided as ulcerative colitis and Crohn's disease. 1 The IBDs are characterized by a strong leukocyte activation and infiltration into the intestinal tissues, the release of proinflammatory cytokines 2 and enzymes, and the formation of reactive oxygen species. All of these events can induce an extensive and unbalanced activation of the mucosal immune system, driven by the commensal flora. 3 Recent evidence suggests a role for the cannabinoid system in IBD regulation. Cannabinoid receptors 1 and 2 (CB1 and CB2) are expressed in normal human colon 4,5 and are up-regulated in IBD colonic tissue. In addition, an enhanced level of endocannabinoids was found in biopsy specimens from patients with ulcerative colitis. 5 It is thought that CB1 activation results in a decrease of intestinal hypermotility and hypersecretion, whereas the activation of CB2 results in the inhibition of proinflammatory mediators. In addition, both CB2 and CB1 knockout mice are more susceptible to the development of experimental colitis, and the activation of these receptors is extremely important for the abrogation of intestinal inflammation. 6 The role of CB2, however, is directly involved with innate immune system, because CB2 is primarily expressed in immune cells, such as macrophages, CD4 ϩ and CD8 ϩ T cells, monocytes, and polymorphonuclear neutro-

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Section: Beneficial Effects Of ␤-Caryophyllene On Dss-induced Colitissupporting

confidence: 88%

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

Bento

Marcon

Dutra

et al. 2011

The American Journal of Pathology

212

145

View full text Add to dashboard Cite

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“…In vivo, CB receptors are activated by arachidonic acid-derived endocannabinoids, such as 2-arachidonoyl ethanolamine (anandamide or AEA) and 2-arachidonoylglycerol (2-AG) (12,13). In addition to a wide range of primarily CB 1 receptor-mediated physiological effects on the central nervous system, different cannabinoid ligands have been reported to modulate immune responses (14). In particular, CB 2 receptor ligands have been shown to inhibit inflammation and edema formation (15), exhibit analgesic effects (16), and play a protective role in hepatic ischemia-reperfusion injury (17).…”

mentioning

confidence: 99%

Beta-caryophyllene is a dietary cannabinoid

Gertsch

Leonti

Raduner

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

724

583

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The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB1) and CB2 receptors. Although the CB1 receptor is responsible for the psychomodulatory effects, activation of the CB2 receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile (E) Cannabis ͉ CB2 cannabinoid receptor ͉ foodstuff ͉ inflammation ͉ natural product P lant essential oils are typically composed of volatile aromatic terpenes and phenylpropanoids. These lipophilic volatiles freely cross cellular membranes and serve various ecological roles, like plant-insect interactions (1, 2). The sesquiterpene (E)-␤-caryophyllene [(E)-BCP] (Fig. 1) is a major plant volatile found in large amounts in the essential oils of many different spice and food plants, such as oregano (Origanum vulgare L.), cinnamon (Cinnamomum spp.) and black pepper (Piper nigrum L.) (3-5). In nature, (E)-BCP is usually found together with small quantities of its isomers (Z)-␤-caryophyllene [(Z)-BCP or isocaryophyllene] and ␣-humulene (formerly ␣-caryophyllene) or in a mixture with its oxidation product, BCP oxide (Fig. 1). Because of its weak aromatic taste, (E)-BCP is commercially used as a food additive and in cosmetics (6). (E)-BCP is also a major component (up to 35%) in the essential oil of Cannabis sativa L (7). Although Cannabis contains Ͼ400 different secondary metabolites, including Ͼ65 cannabinoid-like natural products, only ⌬ 9 -tetrahydrocannabinol (THC), ⌬ 8 -tetrahydrocannabinol, and cannabinol have been reported to activate cannabinoid receptor types 1 (CB 1 ) and 2 (CB 2 ) (8). Here, we show that the essential oil component (E)-BCP selectively binds to the CP55,940 binding site (i.e., THC binding site) in the CB 2 receptor, leading to cellular activation and antiinflammatory effects. CB 1 and CB 2 cannabinoid receptors are GTP-binding protein (G protein) coupled receptors that were first cloned in the early 1990s (9, 10). Although the CB 1 receptor is expressed in the central nervous system and in the periphery, the CB 2 receptor is primarily found in peripheral tissues (11). In vivo, CB receptors are activated by arachidonic acid-derived endocannabinoids, such as 2-arachidonoyl ethanolamine (anandamide or AEA) and 2-arachidonoylglycerol (2-AG) (12, 13). In addition to a wide range of primarily CB 1 receptor-mediated physiological effects on the central nervous system, different cannabinoid ligands have been reported to modulate immune responses (14). In particular, CB 2 receptor ligands have been shown to inhibit inflammation and edema formation (15), exhibit analgesic effects (16), and play a protective role in hepatic ischemia-reperfusion injury (17). In the gastrointestinal tract, CB 2 receptor agonists have been shown to prevent experimental colitis by reducing inflammation (18). Moreover, the CB 2 receptor has been described as a potential ...

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“…The hypothalamic endocannabinoids have been shown to control food intake in both animals and humans, modulating eating behavior thus indicating that alterations of the endocannabinoid system could be involved in the pathophysiology of eating disorders [43,44].…”

Section: Cannabinoids and Eating Disordersmentioning

confidence: 99%

The role of endocannabinoids in the control of eating disorders

Milano¹,

Tecce²,

Capasso³

2017

Dis Disord

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Eating Disorder (ED) is a syndrome characterized by persistent alteration of eating behavior and the conditions that cause an insufficient ingestion and/or adsorption of foods. There are three different ED diseases: Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorders (BED). ED are complex conditions that arise from a combination of long-standing behavioral, emotional, psychological, interpersonal, and social factors. The neuronal circuits that control the ingestion of food are mainly related to catecholaminergic, serotoninergic and peptidergic systems. In this respect, while serotonin, dopamine and prostaglandin promote the ingestion of food, by contrast, neuropeptide Y, norepinephrine, GABA and opioid peptides inhibit food ingestion thus causing the occurrence of ED. The drugs mainly used in the treatment of ED are antidepressants such as selective serotonin reuptake inhibitors and tricyclic antidepressant. Additionally, mood stabilizers (lithium), anxiolytics, serotonin and noradrenalin reuptake inhibitors and antipsychotic drugs are often used in the treatment of ED.Several studies indicate that the endocannabinoid system is involved in ED supporting the idea that the cannabinoid signaling system is a key modulatory element in the activity in the brain area associated with ED.

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Cannabinoid-based drugs as anti-inflammatory therapeutics

Cited by 642 publications

References 114 publications

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

Beta-caryophyllene is a dietary cannabinoid

The role of endocannabinoids in the control of eating disorders

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