scholarly journals Omega-3 Endocannabinoid-Epoxides Are Novel Anti-inflammatory and Anti-Pain Lipid Metabolites (FS15-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Aditi Das ◽  
Josephine Watson ◽  
Lauren Carnevale ◽  
William Arnold
Keyword(s):  
Fatty Acids ◽  
Heart Association ◽  
The Body ◽  
Enzymatic Oxidation ◽  
Enzymatic Reactions ◽  
Cb2 Receptor ◽  
Omega 3 ◽  
Receptor Agonists ◽  
Anti Inflammatory

Abstract Objectives Omega-3 fatty acid derived endocannabinoids are metabolized by cytochrome P450s to form bioactive endocannabinoid epoxides that are anti-inflammatory Methods Lipidomics, LC-MS/MS, microglial cells culture, lipid synthesis, extractions, enzymology Results Cannabinoids are found in marijuana and also are produced naturally in the body from ω-3 and ω-6 fatty acids. Exocannabinoids in marijuana, are known to be responsible for some of its euphoric effects, but they also exhibit anti-inflammatory benefits. Our study revealed a cascade of enzymatic reactions that convert ω-3 fatty acids into anti-inflammatory endocannabinoid epoxides that act through the same receptors in the body as marijuana (PNAS 2017). Endocannabinoids are ligands for cannabinoid receptor 1 and 2 (CB1 and CB2). CB1 receptor agonists exhibit psychotropic properties while CB2 receptor agonists have anti-inflammatory effects. Consequently, there is a strong interest in the discovery of CB2 selective agonists to mitigate inflammatory pathologies. The work details the discovery and characterization of naturally occurring ω-3–derived endocannabinoid epoxides that are formed via enzymatic oxidation of ω-3 endocannabinoids by cytochrome P450 epoxygenases. These dual functional ω-3 endocannabinoid epoxides exhibit preference towards binding to CB2 receptor and are anti-inflammatory and vasodilatory and reciprocally modulate platelet aggregation. Some of the other regioisomers of ω-3 endocannabinoid epoxides are partial agonists of CB1 and stop tumor cell metastasis (J. Med. Chem 2018). By virtue of their physiological properties, they are expected to play important roles in neuroinflammation and pain. Conclusions This finding demonstrates how omega-3 fatty acids can produce some of the same medicinal qualities as marijuana, but without a psychotropic effect. In summary, the ω-3 endocannabinoid epoxides are found at concentrations comparable to those of other endocannabinoids and are expected to play critical roles during inflammation in vivo Funding Sources American Heart Association Scientist Development award, National Institute of Health (NIH) R01, NIH R03, USDA, National Multiple Sclerosis Society.

scholarly journals An Overview of Analeptic Applications of Omega-3 Fatty Acids

2021 ◽  
pp. 95-118
Author(s):  
Bharat Kwatra ◽  
Harsimran Kaur ◽  
Joydip Majumdar ◽  
Mahek Shah ◽  
Mansi Upadhyaya ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Fatty Acids ◽  
Cardiovascular Health ◽  
The Body ◽  
Omega 3 Fatty Acids ◽  
Skin Disorders ◽  
Omega 3 ◽  
Pufa Ratio ◽  
Omega 6 ◽  
Anti Inflammatory

This article is an examination of the Analeptic Applications of Omega-3. The scientific development and subsequent clinical applications of Omega-3 in Healthcare continue to influence researchers all over the globe today. This article examines the research done and published by researchers and scientists. Consideration of current trends and data in scientific queries and demonstrates further aspects of the applications of Omega-3 on various health backgrounds, including. Cardiovascular Health: The study addresses the comparison of Omega-3 and Omega-6 in cardiovascular diseases. Higher intake of dietary Omega-3 helps activation, inhibition, and alteration of metabolic and signaling pathways which is associated with better cardiovascular health, while Omega-6 decreases the risk of coronary heart diseases and cardiovascular disease mortality. Immunology: Omega-3 Polyunsaturated Fatty Acids (PUFAs) have been found to show an anti-inflammatory effect in the body by downregulating the activation of various immune cells. They regulate immunological functions via eicosanoids and resolvins which are anti-inflammatory. External supplementation can reduce chronic and acute inflammation as well as reduce the chances of graft rejection. The regulatory effect is shown by modifying gene expression and/or signal transduction in human cells. They are also involved in altering the membrane composition of Fatty Acids(FA) and as a result, they affect the lipid raft structure and also membrane trafficking. Joint Health: The study shows the effects of omega-3 and other fatty acid consumption in Rheumatoid Arthritis(RA), bone marrow lesions, and knee cartilage lesions. It notes the interrelations between synovitis, plasma levels of Omega-3 and Omega-6 PUFAs in OsteoArthritis (OA) patients along with risk factors for OA, which could help consider liable treatments for improvement of OA. The study highlights the importance of the Omega-6:Omega-3 PUFA ratio and clinical and functional outcome measures which can help us in better understanding the role of PUFAs and possible treatments for people with knee osteoarthritis while showing the effect of Omega-3 fatty acids on muscle health in RA. Skin Disorders: Fish oils rich in PUFAs are reported to improve several inflammatory disorders, including rheumatoid arthritis and psoriasis. They have also been broadly reported as a potential supplement to ameliorate the severity of some skin disorders such as photoaging, skin cancer, allergy, dermatitis, cutaneous wounds, and melanogenesis. The significance of omega-3 in skin structure was proved by describing a syndrome caused by stringent fat reduction in the diet that leads to erythema with scaling, hair loss, itching, and increased water loss.

DEVELOPMENT OF AN EXPERIMENTAL MODEL OF AVITAMINOSIS F

2020 ◽  
Vol 20 (2) ◽  
pp. 38-40
Author(s):  
A. Levitsky ◽  
A. Lapinska ◽  
I. Selivanskaya
Keyword(s):  
Fatty Acids ◽  
Experimental Model ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Coconut Oil ◽  
The Body ◽  
Regulatory Function ◽  
Omega 3 ◽  
White Rats ◽  
Arachidonic Acids

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.

scholarly journals Anti-Platelet Properties of Apple Must/Skin Yeasts and of Their Fermented Apple Cider Products

Beverages ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 54
Author(s):  
Donal Moran ◽  
Mary Fleming ◽  
Eimear Daly ◽  
Natasha Gaughan ◽  
Ioannis Zabetakis ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Platelet Aggregation ◽  
Functional Properties ◽  
Human Platelet ◽  
Omega 3 ◽  
Apple Cider ◽  
Human Platelet Aggregation ◽  
Yeast Strains ◽  
Omega 6 ◽  
Anti Inflammatory

Alcoholic beverages like apple cider are considered functional beverages with several health benefits, when consumed in moderation, which are mainly attributed to their microbiota and the plethora of their bioactive compounds. Among them, bio-functional polar lipids (PL) have recently been found in apple cider, which despite low quantities, have exhibited strong anti-inflammatory and anti-platelet properties, while fermentation seems to affect the functionality of apple cider’s PL bioactives. The aim of the present study was to elaborate yeast strains isolated from the complex mixtures of apple surface and must yeasts for evaluating their effects on the anti-platelet functional properties of PL bioactives from their final fermented apple cider products. First, bio-functional PL were extracted and separated from the biomass of the different isolated apple surface/must yeast strains, and were further assessed for their anti-platelet potency against human platelet aggregation induced by the potent inflammatory and thrombotic mediator platelet-activating factor (PAF), or by a classic platelet agonist like adenosine diphopshate (ADP). Novel functional apple ciders were then produced from the fermentation of apple juice by elaborating the most bioactive and resilient yeast strains isolated from the apple must with optimum fermentation properties. PL bioactives extracted from these novel apple cider products were also further assessed for their anti-platelet properties against both the PAF and ADP pathways of human platelet aggregation. These novel cider products were found to contain PL bioactives with lower IC50 values (~40 μg) and thus increased anti-platelet potency against platelet aggregation induced by PAF and ADP. GC-MS analysis of the PL bioactives extracted from these novel apple ciders showed that apple cider PL bioactives are rich in monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), such as the omega-6 linoleic acid (LA) and the omega-3 alpha linolenic acid (ALA), with favorably lower levels for their omega-6/omega-3 PUFA ratio, which further support the observed strong anti-platelet properties putative anti-inflammatory potency for the apple cider PL bioactives. However, further studies are needed in order to elucidate and fully characterize the apple yeast strains that can be utilized for increasing the anti-inflammatory, anti-platelet and cardioprotective functional properties of their fermented apple cider products.

scholarly journals Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jörg Jerosch
Keyword(s):  
Fatty Acids ◽  
Chondroitin Sulfate ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Collagen Hydrolysate ◽  
Cartilage Metabolism ◽  
Promising Therapeutic Approach ◽  
Anti Inflammatory

Osteoarthritis (OA) is a degenerative joint disease that is characterized by increasing loss of cartilage, remodeling of the periarticular bone, and inflammation of the synovial membrane. Besides the common OA therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the treatment with chondroprotectives, such as glucosamine sulfate, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, or nutrients, such as antioxidants and omega-3 fatty acids is a promising therapeutic approach. Numerous clinical studies have demonstrated that the targeted administration of selected micronutrients leads to a more effective reduction of OA symptoms, with less adverse events. Their chondroprotective action can be explained by a dual mechanism: (1) as basic components of cartilage and synovial fluid, they stimulate the anabolic process of the cartilage metabolism; (2) their anti-inflammatory action can delay many inflammation-induced catabolic processes in the cartilage. These two mechanisms are able to slow the progression of cartilage destruction and may help to regenerate the joint structure, leading to reduced pain and increased mobility of the affected joint.

Abstract 607: Antiarrhythmic Effects Of Omega-3 Fatty Acids And Cyp-eicosanoids In A Murine Atrial Fibrillation Model

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Bastian Spallek ◽  
Christina Westphal ◽  
Anne Konkel ◽  
Gerd Wallukat ◽  
Darryl C Zeldin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acids ◽  
Vehicle Group ◽  
Synthetic Analog ◽  
Omega 3 ◽  
Atrial Fibrosis ◽  
Adrenergic Stimulation ◽  
Connexin 40 ◽  
Normal Chow

Atrial fibrillation (AF) is the most common arrhythmia in man. Small animal models of AF are rare, limiting the opportunities of mechanistic studies and of evaluating novel treatment strategies. We found that mice can be rendered susceptible to AF by chronic ß-adrenergic stimulation and used this model to test the hypothesis that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) and endogenously produced cytochrome P450 (CYP)-dependent epoxyeicosanoids protect against AF. Our study included male wild type C57BL/6 mice given either normal chow (WT-n6-group) or a diet supplemented with n-3 PUFAs (2.5% EPA/DHA added to normal chow; WT-n3-group), as well as transgenic littermates with cardiomyocyte-specific overexpression of the human epoxygenase CYP2J2 (CYP-n6 group). All animal groups received 40mg/kg/d of isoproterenol (ISO) or vehicle over 14 days via osmotic mini-pumps. AF induction was tested in vivo by programmed electrical stimulation (PES) and reached 48% (13 of 27 protocols) in ISO-treated WT-n6, compared to 9% (2 of 22) in the vehicle group. ISO-treated WT-n6 mice also featured increased atrial fibrosis, decreased atrial connexin-40 expression, and significantly reduced atrial refractoriness (AERP: 13.1±0.5 vs. 21.7±0.9 ms in vehicle-infused controls). Ventricular refractoriness remained unchanged and ventricular arrhythmias were not inducible. EPA/DHA-supplementation as well as CYP2J2 overexpression significantly reduced ISO-stimulated AF inducibility to 17% (5 of 30 in WT-n3, and 4 of 24 in CYP-n6), decreased atrial fibrosis, and partially prevented connexin-40 down-regulation and AERP reduction (16,1±0,9 in WT-n3 and 17.5±0.5 ms in CYP-n6). Finally, we tested the antiarrhythmic potential of a synthetic analog of 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), an EPA metabolite predominantly produced by CYP2J2 and other epoxygenases. Acute i.v. injection of the 17,18-EEQ compound decreased AF inducibility in ISO-stimulated WT-n6 mice from 67% (14 of 21 in vehicle control) to 33% (10 of 30) and also the mean duration of AF episodes. These results show that ISO-infusion allows establishing a suitable mouse model of AF and indicate an important role of CYP-dependent n-3 PUFA metabolites in preventing AF.

scholarly journals Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769225 ◽  
Author(s):  
Nahla E El-Ashmawy ◽  
Eman G Khedr ◽  
Hoda A El-Bahrawy ◽  
Samar M Al-Tantawy
Keyword(s):  
Fatty Acids ◽  
Bladder Cancer ◽  
Polyunsaturated Fatty Acids ◽  
Molecular Mechanisms ◽  
Combined Treatment ◽  
Lipid Peroxidation Product ◽  
Apoptotic Bodies ◽  
Omega 3 ◽  
Chemopreventive Effect ◽  
Anti Inflammatory

Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as adjuvant therapy with other chemotherapeutics.

scholarly journals α- Linolenic Acid Modulates Phagocytosis of Extracellular Tau and Induces Microglial Migration

2020 ◽  
Author(s):  
Smita Eknath Desale ◽  
Subashchandrabose Chinnathambi
Keyword(s):  
Fatty Acids ◽  
Cell Membrane ◽  
Linolenic Acid ◽  
Dietary Fatty Acids ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Microtubule Organizing Center ◽  
Intracellular Degradation ◽  
Organizing Center ◽  
Anti Inflammatory

Abstract Background The seeding effect of extracellular Tau species is an emerging aspect to study the Tauopathies in Alzheimer’s disease. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. Omega-3 fatty acids are known to exert the anti-inflammatory property to microglia by modulating cell membrane compositions. The immunomodulatory function of omega-3 fatty acids exerts anti-inflammatory properties to microglia. Owing to the imparted anti-inflammatory nature enhance phagocytosis and increased migration property has been observed in microglia. The dietary omega-3 fatty acids are found to change the lipid composition of the cell membrane that predominated many signaling cascades and by modulating specific receptor response. Thus the omega-3 fatty acids influence microglial response in Tauopathy. Methods N9 microglia cells were exposed to extracellular full-length Tau monomer and aggregates along with ALA (α- Linolenic acid) to study the internalization of exposed Tau. The degradation of internalized Tau studied with the endosomal markers Rab5 and Rab7. The final degradation step in phagocytosis has been studied with LAMP-2A as lysosomal markers. The changes in the rate of migration of microglia were assessed by wound-scratch assay along with Microtubule organizing center (MTOC) reorientation were studied after exposure of Tau and ALA as the property of highly migratory microglia. Results The increased phagocytosis of extracellular Tau monomer and aggregates has been observed upon ALA exposure to microglia cells. The intracellular degradation of internalized Tau species was targeted by early and late endosomal markers Rab5 and Rab7. The increased levels of LAMP-2A and colocalization with internalized Tau indicated the degradation via lysosome. These results indicate the degradation of internalized Tau species in the presence of ALA instead of getting accumulated in the cell. The enhanced migratory ability of microglia in the presence of ALA induces the MTOC repolarization and reduces the nuclear-centrosomal axis polarity and favorable anterior positioning of MTOC. Conclusions Tau seeds greatly contribute to the spread of disease, one way to reduce the spreading is to reduce the presence of extracellular Tau seed. Microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids. Our results suggest that dietary fatty acids ALA significantly enhances phagocytosis and intracellular degradation of internalized Tau. Enhanced migration supports the phagocytosis process. Our approach provides insights into the beneficial role of ALA as an anti-inflammatory dietary supplement to treat AD.

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