n−3 polyunsaturated N-acylethanolamines are CB2 cannabinoid receptor-preferring endocannabinoids

Alharthi, Nahed S.; Christensen, Peter; Hourani, Wafa; Ortori, Catharine A.; Barrett, David A.; Bennett, Andrew J.; Chapman, Victoria; Alexander, Stephen P.H.

doi:10.1016/j.bbalip.2018.08.003

Cited by 23 publications

(23 citation statements)

References 52 publications

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“…Thus far, DHA-EA and EPA-EA possess anti-proliferative as well as anti-inflammatory properties and may be key modulators of the inflammatory cascade. Additionally, DHA-EA and EPA-EA possess some affinity to CB and non-CB receptors (Table 1) (19, 20, 62). Although we focus on the nutritionally relevant omega-3 derived eCBs, from DHA and EPA, it is important to highlight reports that have demonstrated that similar analogues, such as α-linolenoyl ethanolamine (ALA-EA), possess pharmacological significance through activation of transient receptor potential vanilloid 1 (TRPV1) and not CB 1 (28, 63).…”

Section: Omega-3 Fatty Acid Epa Ethanolamide (Epa-ea or Epea)mentioning

confidence: 99%

Emerging class of omega-3 fatty acid endocannabinoids & their derivatives

Watson

Kim

Das

2019

Prostaglandins & Other Lipid Mediators

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Cannabinoid receptor activation is involved in homeostatic regulation of the body. These receptors are activated by cannabinoids, that include the active constituents of Cannabis sativa as well as endocannabinoids (eCBs). The eCBs are endogenously synthesized from the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). The consumption of omega-3 fatty acids shifts the balance towards a higher proportion of omega-3 eCBs, whose physiological functions warrants further investigation. Herein, we review the discovery of omega-3 fatty acid derived eCBs that are generated from long chain omega-3 PUFAs - docosahexaenoyl ethanolamide (DHA-EA or synaptamide), docosahexanoyl-glycerol (DHG), eicosapentaenoyl ethanolamide (EPA-EA), eicosapentanoylglycerol (EPG). Furthermore, we outline the lesser known omega-3 eCB-like molecules that arise from the conjugation of the omega-3 fatty acids with neurotransmitters serotonin and dopamine - DHA-serotonin (DHA-5HT), EPA-serotonin (EPA-5HT), DHA-dopamine (DHA-DA) and EPA-dopamine (EPA-DA). Additionally, we describe the role of these omega-3 eCBs and their derivatives in different disease states such as pain, inflammation and cancer. Moreover, we detail the formation and potential physiological roles of the oxidative metabolites that arise from the metabolism of omega-3 eCBs by eicosanoid synthesizing enzymes - cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 epoxygenase (CYP450). In summary, we outline the novel findings regarding a growing class of signaling molecules, omega-3 eCBs, that can control the physiological and pathophysiological processes in the body.

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Section: Omega-3 Fatty Acid Epa Ethanolamide (Epa-ea or Epea)mentioning

confidence: 99%

Emerging class of omega-3 fatty acid endocannabinoids & their derivatives

Watson

Kim

Das

2019

Prostaglandins & Other Lipid Mediators

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“…The discovery of CB receptors throughout the human body prompted the search for innate compounds that serve to activate these receptors (Zou & Kumar, 2018 by local precursors within the cell and cell membrane (Di Marzo et al, 1994). A large number of endocannabinoids have been identified including n-3 and n-6 polyunsaturated fatty acid N-acylethanolamines and monoacylglycerols (Alharthi et al, 2018;Battista et al, 2012). Of all the endocannabinoids, anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol (2-AG) are the most commonly researched (Battista et al, 2012;Howlett et al, 2002).…”

Section: Endocannabinoidsmentioning

confidence: 99%

Cannabinoid control of neurogenic inflammation

McKenna

McDougall

2020

British J Pharmacology

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A significant number of cannabinoids are known to have analgesic and anti‐inflammatory properties in various diseases. Due to their presynaptic/terminal location, cannabinoid receptors can inhibit synaptic transmission and have the potential to regulate neurogenic inflammation. Neurogenic inflammation occurs when a noxious signal is detected in the periphery initiating an antidromic axon reflex in the same sensory neurone leading to depolarization of the afferent terminal. Neuropeptides are subsequently released and contribute to vasodilation, plasma extravasation and modulation of immune cells. Endocannabinoids, synthetic cannabinoids and phytocannabinoids can reduce neuroinflammation by inhibiting afferent firing and inflammatory neuropeptide release. Thus, in addition to a direct effect on vascular smooth muscle and inflammatory cells, cannabinoids can reduce inflammation by silencing small diameter neurones. This review examines the neuropharmacological processes involved in regulating antidromic depolarization of afferent nerve terminals by cannabinoids and the control of neurogenic inflammation in different diseases.

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“…However, inflammation is a complex process in which different receptors, signaling pathways, and transcription factors are involved. Indeed, n-3 PUFA amides possess some affinity to CBs and non-CB receptors, such as GPRs, TRVP1, and PPARs [66][67][68]. Interestingly, among PPARs that are members of the nuclear receptor superfamily and function as ligand-activated transcription factors [69], PPARγ is a subset of the PPAR family, mainly expressed in adipose tissue, mammary gland, colon, and the immune system [70,71].…”

Section: N-acylserotonin Dha-5htmentioning

confidence: 99%

n–3 Polyunsaturated Fatty Acid Amides: New Avenues in the Prevention and Treatment of Breast Cancer

Giordano

Plastina

Barone

et al. 2020

IJMS

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Over the last decades a renewed interest in n−3 very long polyunsaturated fatty acids (PUFAs), derived mainly from fish oils in the human diet, has been observed because of their potential effects against cancer diseases, including breast carcinoma. These n−3 PUFAs mainly consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that, alone or in combination with anticancer agents, induce cell cycle arrest, autophagy, apoptosis, and tumor growth inhibition. A large number of molecular targets of n−3 PUFAs have been identified and multiple mechanisms appear to underlie their antineoplastic activities. Evidence exists that EPA and DHA also elicit anticancer effects by the conversion to their corresponding ethanolamide derivatives in cancer cells, by binding and activation of different receptors and distinct signaling pathways. Other conjugates with serotonin or dopamine have been found to exert anti-inflammatory activities in breast tumor microenvironment, indicating the importance of these compounds as modulators of tumor epithelial/stroma interplay. The objective of this review is to provide a general overview and an update of the current n−3 PUFA derivative research and to highlight intriguing aspects of the potential therapeutic benefits of these low-toxicity compounds in breast cancer treatment and care.

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n−3 polyunsaturated N-acylethanolamines are CB2 cannabinoid receptor-preferring endocannabinoids

Cited by 23 publications

References 52 publications

Emerging class of omega-3 fatty acid endocannabinoids & their derivatives

Emerging class of omega-3 fatty acid endocannabinoids & their derivatives

Cannabinoid control of neurogenic inflammation

n–3 Polyunsaturated Fatty Acid Amides: New Avenues in the Prevention and Treatment of Breast Cancer

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