Antiinflammatory cannabinoids in diet – towards a better understanding of CB2 receptor action?

Gertsch, Jürg

doi:10.4161/cib.1.1.6568

Cited by 88 publications

(66 citation statements)

References 35 publications

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“…The system is able to downregulate stress-related signals that lead to chronic inflammation and certain types of pain, but it is also involved in causing inflammation-associated symptoms, depending on the physiological context.”32…”

Section: The Endocannabinoid System: Receptors and Endogenous Receptomentioning

confidence: 99%

The Endocannabinoid System, Cannabinoids, and Pain

Fine¹,

Rosenfeld²

2013

Rambam Maimonides Med J

121

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The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not exclusively CB1 receptors) and in the periphery (primarily but not exclusively CB2 receptors) are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions. Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain.

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Section: The Endocannabinoid System: Receptors and Endogenous Receptomentioning

confidence: 99%

The Endocannabinoid System, Cannabinoids, and Pain

Fine¹,

Rosenfeld²

2013

Rambam Maimonides Med J

121

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“…cinnamon, origanum, black pepper, basil and cloves) and food/medicinal plants[1, 2]. BCP is also often used in cosmetics and is an FDA-approved food additive and component of Cannabis sativa and Sativex, an approved drug in European countries and in Canada[3].…”

Section: Introductionmentioning

confidence: 99%

β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner

Horváth

Mukhopadhyay

Kechrid

et al. 2012

Free Radical Biology and Medicine

Self Cite

118

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(E)-β-caryophyllene (BCP) is a natural sequiterpene found in many essential oils of spice (best known for contributing to the spiciness of black pepper) and food plants with recognized anti-inflammatory properties. Recently it was shown that BCP is a natural agonist of endogenous cannabinoid 2 (CB2) receptors, which are expressed in immune cells and mediate anti-inflammatory effects. In this study we aimed to test the effects of BCP in a clinically relevant murine model of nephropathy (induced by the widely used antineoplastic drug cisplatin) in which the tubular injury is largely dependent on inflammation and oxidative/nitrative stress. β-caryophyllene dose-dependently ameliorated cisplatin-induced kidney dysfunction, morphological damage, and renal inflammatory response (chemokines MCP-1 and MIP-2, cytokines TNF-α and IL-1β, adhesion molecule ICAM-1, and neutrophil and macrophage infiltration). It also markedly mitigated oxidative/nitrative stress (NOX-2, NOX-4 expression, 4-HNE and 3-NT content) and cell death. The protective effects of BCP against biochemical and histological markers of nephropathy were absent in CB2 knockout mice. Thus, BCP may be an excellent therapeutic agent to prevent cisplatin-induced nephrotoxicity through a CB2 receptor dependent pathway. Given the excellent safety profile of BCP in humans it has tremendous therapeutic potential in multitude of diseases associated with inflammation and oxidative stress.

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“…BCP could inhibit the pathways triggered by the activation of the Toll-like receptor complex CD14/TLR4/MD2, which typically leads to the expression of proinflammatory cytokines (IL-1␤, IL-6, IL-8, and TNF-␣). 24 In addition, BCP suppresses extracellular signalregulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) signaling. All of these effects contribute to the anti-inflammatory effects of the sesquiterpene.…”

mentioning

confidence: 99%

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

204

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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Antiinflammatory cannabinoids in diet – towards a better understanding of CB2 receptor action?

Cited by 88 publications

References 35 publications

The Endocannabinoid System, Cannabinoids, and Pain

The Endocannabinoid System, Cannabinoids, and Pain

β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner

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

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