An In Silico Comparative Study of Anti-inflammatory Role of Biochanin A and Genistein with 9 Omega-3-fatty Acids Using Complex Docking Analysis with PPARγ and GPR120

Abstract Background Tau seeds exhibit a detrimental role in the spread of disease in Alzheimer’s disease. These species are found to be neurotoxic and activate microglia. However, the activation of microglia in pro-inflammatory response further elevates neurodegeneration. Omega-3 dietary fatty acids, on the other hand; exert an anti-inflammatory response by microglia. Along with the receptor expression, omega-3 fatty acids influence various important cellular functions. The role of omega-3 fatty acids on actin remodeling, which is the basis of cellular functions such as migration and phagocytosis is not known. Here in this study, we focus on effect of dietary supplement of ALA on extracellular Tau internalization and assisted actin polymerization for the process. ALA is found to induce membrane ruffling and phagocytic cup formation along with cytoskeletal rearrangement to induce lamellipodia and filopodia at the front end to move forward and assist the cell to identify the target. ALA is observed to promote the internalization of Tau and necessary actin remodeling for phagocytosis. Methods α-Linolenic (ALA) acid has been used for the study. ALA was dissolved in 100% ethanol and solubilized at 50°C for 2 hours. The human Tau aggregates was prepared in vitro for the internalization study in microglia in presence of α-Linolenic acids (ALA) via fluorescence microscopy with Apotome. The studied the role α-Linolenic acids (ALA) actin remodeling in cellular processes in presence of Tau seed. The study of actin structures lamellipodia, filopodia, and membrane ruffling along with Iba-1 and Arp2/3 complex was observed on ALA exposure. Results Extracellular Tau species are found to internalize more presence of ALA in microglia. The extensive polarization and migration was observed as indicated by extensive lamellipodia and filopodia formation. The formation of extensive actin branching in lamellipodia and membrane ruffling was studied with the help of ARP2/3 complex for nucleating actin network. The high density of ARP2/3 complex at the leading ends of migratory microglia confirmed the extensive branching of actin filaments on ALA exposure. Enhanced formation of lamellipodia and filopodia helps in migration and internalization of tau seed. The actin dynamics supports the phagocytosis process. Conclusion Our approach provides the insights of beneficial role of ALA as anti-inflammatory dietary supplement to treat AD. ALA induces internalization of Tau and necessary actin remodeling for phagocytosis.

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Role of Omega-3 Fatty Acids and Butter Oil in Targeting Delivery of Donepezil Hydrochloride Microemulsion to Brain via the Intranasal Route: a Comparative Study

AAPS PharmSciTech ◽

10.1208/s12249-019-1585-7 ◽

2020 ◽

Vol 21 (2) ◽

Cited By ~ 2

Author(s):

Dignesh Khunt ◽

Meenakshee Shrivas ◽

Suryanarayana Polaka ◽

Piyush Gondaliya ◽

Manju Misra

Keyword(s):

Fatty Acids ◽

Comparative Study ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Intranasal Route ◽

Butter Oil ◽

Targeting Delivery ◽

Donepezil Hydrochloride

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α- Linoleanic acid modulates phagocytosis of extracellular Tau and induces microglial migration by actin-remodeling

10.21203/rs.3.rs-22830/v1 ◽

2020 ◽

Author(s):

Smita Eknath Desale ◽

Subashchandrabose Chinnathambi

Keyword(s):

Fatty Acids ◽

Cell Membrane ◽

Dietary Fatty Acids ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Actin Remodeling ◽

Membrane Ruffling ◽

Intracellular Degradation ◽

Anti Inflammatory

Abstract Background 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 property 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 cascade and by modulating specific receptor response. Thus the omega-3 fatty acids influence microglial response in Tauopathy.Method 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. The role of actin in phagocytosis and migration was observed with the study of actin structures lamellipodia, filopodia, and membrane ruffling. The formation of extensive actin branching in lamellipodia and membrane ruffling was studied with the help of ARP2/3 complex for nucleating actin network.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 increase 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. The increased migration also complememnted with the enhance actin remodeling through lamellipodia, filopodia and membrane ruffles formation along with Iba-1 protein. The high desnity of ARP2/3 complex at the leading ends of migratory microglia confirmed the extensive branching of actin filaments on ALA exposure.Conclusions Tau seeds greatly contributes 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 enhance phagocytosis and intracellular degradation of internalized Tau. The actin dynamics and enhanced migration supports the phagocytosis process. Our approach provides the insights of beneficial role of ALA as anti-inflammatory dietary supplement to treat AD.

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α-Linolenic acid modulates phagocytosis of extracellular Tau and induces microglial migration

10.1101/2020.04.15.042143 ◽

2020 ◽

Author(s):

Smita Eknath Desale ◽

Subashchandrabose Chinnathambi

Keyword(s):

Fatty Acids ◽

Dietary Fatty Acids ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Intracellular Degradation ◽

Seeding Effect ◽

Microglial Migration ◽

Anti Inflammatory ◽

Immunomodulatory Function

AbstractThe 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 that influence various receptors expression and signaling cascade. 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 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. 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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The potential role of omega-3 fatty acids supplements in increasing athletic performance

Timisoara Physical Education and Rehabilitation Journal ◽

10.1515/tperj-2016-0004 ◽

2016 ◽

Vol 9 (16) ◽

pp. 25-34

Author(s):

Șerban Gligor ◽

Răzvan Gligor

Keyword(s):

Physical Activity ◽

Fatty Acids ◽

Athletic Performance ◽

Potential Role ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Omega 6 ◽

Anti Inflammatory ◽

Inflammatory Effect

Abstract Polyunsaturated omega-3 and omega-6 fatty acids are essential fatty acids that cannot be produced by the body itself and therefore must be provided through nutrition. Omega-6 and particularly omega-3 fatty acids have important roles in the organism, contributing to the maintenance and promotion of health. The optimal proportion of omega-6/omega-3 fatty acids is 2:1, or even better 1:1. They are involved in normal growth and development, play a role in the prevention of coronary and cardiovascular diseases, of diabetes mellitus, of arterial hypertension, arthritis and cancer. Omega-3 fatty acids mainly have an anti-inflammatory effect, but also act as hypolipidemic and antithrombotic agents. A potential role of omega-3 fatty acids is that of increasing physical performance. Their role in the physical activity refers on one side to the global health of athletes and on the other side to their anti-inflammatory effect, as high intensity physical exercise induces increased free-radical production and microtraumas, with the induction of an inflammatory status. The anti-inflammatory effect of these fatty acids manifests through an increased production of endogenous antioxidant enzymes, through decreasing the production of prostaglandins metabolites, decreasing the production of leukotriene B4, etc. They are also effective on reducing muscle pain post eccentric exercise and on decreasing the severity of bronchoconstriction induced by exercise, as well as improving pulmonary function variables. In conclusion it seems that supplementing diets with omega-3 fatty acids, apart from having benefic effects on health and on the prevention and management of certain affections, proves to be a beneficial for physical activity and athletic performance.

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The role of l-carnitine and omega-3 fatty acids in prevent meiotic damages to bovine oocytes matured in vitro with follicular fluid from womem with different stages of endometriosis

Fertility and Sterility ◽

10.1016/j.fertnstert.2018.07.1108 ◽

2018 ◽

Vol 110 (4) ◽

pp. e396-e397

Author(s):

V.S. Giorgi ◽

R.A. ferriani ◽

P. Navarro

Keyword(s):

Fatty Acids ◽

Follicular Fluid ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Bovine Oocytes

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Comparative study of tissue deposition of omega-3 fatty acids from polar-lipid rich oil of the microalgae Nannochloropsis oculata with krill oil in rats

Food & Function ◽

10.1039/c4fo00591k ◽

2015 ◽

Vol 6 (1) ◽

pp. 185-191 ◽

Cited By ~ 27

Author(s):

Michael L. Kagan ◽

Aharon Levy ◽

Alicia Leikin-Frenkel

Keyword(s):

Fatty Acids ◽

Comparative Study ◽

Polar Lipid ◽

Rat Plasma ◽

Nannochloropsis Oculata ◽

Polar Lipids ◽

Omega 3 Fatty Acids ◽

Krill Oil ◽

Omega 3 ◽

Epa And Dha

An oil from micro-algae rich in EPA with no DHA and consisting of 15% polar lipids (phospholipids and glycolipids) showed equivalent uptake of EPA into rat plasma and organs as omega-3 krill oil consisting of EPA and DHA and 40% phospholipids.

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

International Journal of Rheumatology ◽

10.1155/2011/969012 ◽

2011 ◽

Vol 2011 ◽

pp. 1-17 ◽

Cited By ~ 67

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.

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