Polar lipids modify Alzheimer's Disease pathology by reducing astrocyte pro-inflammatory signaling through platelet-activating factor receptor (PTAFR) modulation.

BACKGROUND: Pro-inflammatory processes triggered by the accumulation of extracellular amyloid beta (Aß) peptides are a well-described pathology in Alzheimer's disease (AD). Activated astrocytes surrounding Aß plaques contribute to inflammation by secreting proinflammatory factors. While astrocytes may phagocytize Aß and contribute to Aß clearance, reactive astrocytes may also increase Aß production. Therefore, identifying factors that can attenuate astrocyte activation and neuroinflammation and how these factors influence pro-inflammatory pathways is important for developing therapeutic and preventive strategies in AD. Here, we identify the platelet-activating factor receptor (PTAFR) pathway as a key mediator of astrocyte activation. Intriguingly, several polar lipids (PLs) have exhibited anti-inflammatory protective properties outside the central nervous system through their inhibitory effect on the PTAFR pathway. Thus, we additionally investigated whether different PLs also exert inhibitory effects on the PAF pathway in astrocytes and whether their presence influences astrocytic pro-inflammatory signaling and known AD pathologies in vitro. METHODS: PLs from salmon and yogurt were extracted using novel food-grade techniques and their fatty acid profile was determined using LC/MS. The effect of PLs on parameters such as astrocyte activation and generation of oxygen species (ROS) was assessed. Additionally, effects of the secretome of astrocytes treated with these polar lipids on aged neurons was measured. RESULTS: We show that PLs obtained from salmon and yogurt lower astrocyte activation, the generation of reactive oxygen species (ROS), and extracellular Aß accumulation. Cell health of neurons exposed to the secretome of astrocytes treated with salmon-derived PLs and Aß was less affected than those treated with astrocytes exposed to Aß only. CONCLUSION: Our results highlight a novel underlying mechanism, why consuming PL-rich foods such as fish and dairy may reduce the risk of developing dementia and associated disorders.

Cardiovascular Diseases and Marine Oils: A Focus on Omega-3 Polyunsaturated Fatty Acids and Polar Lipids.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFAs regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFAs. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

Oil from Mullet Roe Byproducts: Effect of Oil Extraction Method on Human Erythrocytes and Platelets.

Background: The valorization of byproducts to obtain high nutritional value foods is of utmost importance for our planet where the population is booming. Among these products are oils rich in ω-3 fatty acids produced from fishery byproducts. Recently, mullet roe oil from roe byproducts was produced that was rich in the ω-3 fatty acids eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA). Oils are customarily characterized for their composition and degree of oxidation but little is known of their biological effects, especially the effect of the extraction method. Methods: The purpose of this study was to evaluate the effects of freshly extracted mullet roe oil from mullet roe byproducts and the effect of the extraction method on human red blood cells (hRBCs) and platelets. To this end, the hemocompatibility (cytotoxicity), oxidative effects, and erythrocyte membrane changes were examined after 1 and 24 h of incubation. Antiplatelet effects were also assessed in vitro. Results: The expeller press oil extraction method and alcalase-assisted extraction produced the most biocompatible oils, as shown by hemocompatibility measurements and the absence of erythrocyte membrane alterations. Solvent extracts and protease-assisted extraction oils resulted in the rupture of red blood cells at different examined dilutions, creating hemolysis. Conclusions: It seems that the proper functioning of oil-erythrocyte interactions cannot be explained solely by ROS. Further investigations combining chemical analysis with oil-cell interactions could be used as an input to design high nutritional value oils using green extraction technologies. All samples exhibited promising antiplatelet and antiblood clotting effects in vitro.

The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease.

Neurodegenerative diseases are a group of disorders characterised by progressive loss of brain function. The most common of these is Alzheimer's disease, a form of dementia. Intake of macro- and micro-nutrients impacts brain function, including memory, learning, mood, and behaviour. Lipids, particularly phospholipids and sphingolipids, are crucial structural components of neural tissues and significantly affect cognitive function. The importance of functional foods in preventing cardiovascular disease is well-documented in the current literature. However, the significance of such foods for central nervous system health and neurodegenerative diseases is less recognized. Gut microbiome composition affects cognitive health and function, and dietary lipids are known to influence gut health. Thus, this review will discuss different sources of dietary lipids and their effect on cognitive functioning and their interaction with the gut microbiome in the context of neurodegenerative disease.

Targeting the Platelet-Activating Factor Receptor (PAF-R): Antithrombotic and Anti-Atherosclerotic Nutrients.

Platelet-activating factor (PAF) is a lipid mediator that interacts with its receptor (PAF-R) to carry out cell signalling. However, under certain conditions the binding of PAF to PAF-R leads to the activation of pro-inflammatory and prothrombotic pathways that have been implicated in the onset and development of atherosclerotic cardiovascular diseases (CVD) and inflammatory diseases. Over the past four decades, research has focused on the identification and development of PAF-R antagonists that target these inflammatory diseases. Research has also shown that dietary factors such as polar lipids, polyphenols, and other nutrient constituents may affect PAF metabolism and PAF-R function through various mechanisms. In this review we focus on the inhibition of PAF-R and how this may contribute to reducing cardiovascular disease risk. We conclude that further development of PAF-R inhibitors and human studies are required to investigate how modulation of the PAF-R may prevent the development of atherosclerotic cardiovascular disease and may lead to the development of novel therapeutics.

Cadmium: A Focus on the Brown Crab (Cancer pagurus) Industry and Potential Human Health Risks.

Cadmium is a major health risk globally and is usually associated with pollution and anthropogenic activity. The presence of cadmium in food is monitored to ensure that the health and safety of consumers are maintained. Cadmium is ubiquitous in the Asian and Western diets, with the highest levels present in grains, leafy greens, and shellfish. As part of their natural lifecycle of moulting and shell renewal, all crustaceans-including the brown crab (Cancer pagurus)-bioaccumulate cadmium from their environment in their hepatopancreas. The brown crab is an important species to the crab-fishing industries of many European countries, including Ireland. However, the industry has come under scrutiny in Europe due to the presence of cadmium in the brown crab meat intended for live export to Asia. This review explores evidence regarding the effects of cadmium consumption on human health, with a focus on the brown crab. Differences in cadmium surveillance have given rise to issues in the crab industry, with economic consequences for multiple countries. Currently, evidence suggests that brown crab consumption is safe for humans in moderation, but individuals who consume diets characterised by high levels of cadmium from multiple food groups should be mindful of their dietary choices.

Cardio-Protective Properties and Health Benefits of Fish Lipid Bioactives; The Effects of Thermal Processing.

The beneficial effects of fish-derived lipid bioactives have come to prominence over the last few decades, especially for their utilization in fish oils, supplements, and nutraceuticals. Omega-3 (n-3) polyunsaturated fatty acids (PUFA), lipid vitamins, carotenoids, and polar lipid bioactives from fish have shown to possess a vast range of beneficial effects against a multitude of chronic disorders and especially against inflammation-and cardiovascular disorders (CVD). The observed cardio-protective effects and health benefits are believed to be attributed to the synergy of these fish-derived lipid bioactives. Within the present article the recent findings in the literature on the lipid content of the mainly consumed fish species, their bio-functionality, and cardio-protective benefits is thoroughly reviewed. Moreover, the recovery and valorization of such lipid bioactives from fish by-products and fishing by-catch, in order to reduce waste, while developing useful products containing cardio-protective lipids from the leftover materials of fisheries and aquaculture industries, are also of industrial and environmental interest. Emphasis is also given to the effects of heat treatments during fish processing on the structures and bio-functionality of these marine lipid bioactives, based on the paradigm of different cooking methodologies and thermal processing, while the compounds produced during such treatment(s) with detrimental changes in the fish lipid profile, which can reduce its cardio-protective efficacy, are also reviewed. Novel green extraction technologies and low temperature processing and cooking of fish and fishery by-products are needed to reduce these undesirable effects in a sustainable and environmentally friendly way.

Investigation of Platelet Aggregation in Atherosclerosis.

Platelet activation and aggregation is implicated in all stages of inflammation-related atherosclerosis from the initial steps of endothelial dysfunction and plaque formation, to plaque rupture and atherothrombotic events, such as acute coronary syndrome, myocardial infarction, and ischemic incidences. Platelet aggregometry assays are the mainstream for evaluating and monitoring platelet reactivity in such conditions and for the investigation of prophylactic and therapeutic approaches. The most established methodology is light transmittance aggregometry (LTA). Here we describe the appropriate preparation of platelet suspensions from human blood and the methodology of LTA-based assays that is used for basic and clinical research for monitoring and evaluating the activities of several thrombotic mediators, as well as determining the dose efficacy and safety of several pharmaceutical and nutraceutical compounds intended for therapeutic and prophylactic interventions for atherosclerosis.

The Role of an Anti-Inflammatory Diet in Conjunction to COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), otherwise known as COVID-19, has challenged healthcare systems at an international level. COVID-19 suppresses the immune system by causing a systemic inflammatory response, also known as cytokine release syndrome, leaving COVID-19 patients with high levels of proinflammatory cytokines and chemokines. Nutrition's function in the respiratory and immune systems has been investigated in much research, and its significance cannot be overstated, as the nutritional status of patients has been shown to be directly connected with the severity of the disease. Key dietary components such as vitamin C, D, omega-3 fatty acids, and zinc have shown potential in their anti-inflammatory effects, as well as the famous Mediterranean diet. This review aims to discuss the use of anti-inflammatory dietary approaches to prevent Sars-CoV-2 or lessen COVID-19 effects.

Microalgal Lipid Extracts Have Potential to Modulate the Inflammatory Response: A Critical Review.

Noncommunicable diseases (NCD) and age-associated diseases (AAD) are some of the gravest health concerns worldwide, accounting for up to 70% of total deaths globally. NCD and AAD, such as diabetes, obesity, cardiovascular disease, and cancer, are associated with low-grade chronic inflammation and poor dietary habits. Modulation of the inflammatory status through dietary components is a very appellative approach to fight these diseases and is supported by increasing evidence of natural and dietary components with strong anti-inflammatory activities. The consumption of bioactive lipids has a positive impact on preventing chronic inflammation and consequently NCD and AAD. Thus, new sources of bioactive lipids have been sought out. Microalgae are rich sources of bioactive lipids such as omega-6 and -3 polyunsaturated fatty acids (PUFA) and polar lipids with associated anti-inflammatory activity. PUFAs are enzymatically and non-enzymatically catalyzed to oxylipins and have a significant role in anti and pro-resolving inflammatory responses. Therefore, a large and rapidly growing body of research has been conducted in vivo and in vitro, investigating the potential anti-inflammatory activities of microalgae lipids. This review sought to summarize and critically analyze recent evidence of the anti-inflammatory potential of microalgae lipids and their possible use to prevent or mitigate chronic inflammation.

Anti-Inflammatory and Anti-Platelet Properties of Lipid Bioactives from Apple Cider By-Products.

The valorization of food industry by-products as sources of bioactive compounds is at the forefront of research in functional foods and nutraceuticals. This study focuses on bioactives of apple cider by-products (ACBPs) with putative cardio-protective properties. Total lipids (TLs) were extracted from ACBPs of apple varieties that are low (ACBP1), medium (ACBP2), and high (ACBP3) in tannins and were further separated into polar lipids (PLs) and neutral lipids (NLs). The functionality of these lipid extracts and of their HPLC-derived lipid fractions/PL subclasses were assessed in vitro against human platelet aggregation induced by the thrombotic and inflammatory platelet agonists platelet-activating factor (PAF) and adenosine diphosphate (ADP). The fatty acid profile of PLs and their most bioactive lipid fractions were evaluated by GC-MS analysis. The PL extracts exhibited higher specificity against the PAF-induced platelet aggregation compared to their anti-ADP effects, while TL and NL showed lower bioactivities in all ACBPs. HPLC analysis unveiled that the most bioactive PL from all ACBPs were those in PL fraction 3 containing phosphatidylcholines (PCs). PLs from all ACBPs and their PC bioactives were rich in polyunsaturated fatty acids (PUFAs) and especially in the essential omega-6 (n-6) linoleic acid (LA) and omega-3 (n-3) alpha linolenic acid (ALA), with favorably low values of the n-6/n-3 PUFA ratio, thus providing a rationale for their higher anti-inflammatory bioactivities. Within this study, highly bioactive PL compounds with strong anti-inflammatory and anti-platelet properties were identified in ACBPs, which can be potentially utilized for producing cardio-protective functional foods and/or nutraceuticals.

Beneficial Anti-Platelet and Anti-Inflammatory Properties of Irish Apple Juice and Cider Bioactives.

Several bioactives from fruit juices and beverages like phenolics, nucleotides and polar lipids (PL) have exhibited anti-platelet cardio-protective properties. However, apple juice and cider lipid bioactives have not been evaluated so far. The aim of this study was to investigate the anti-platelet and anti-inflammatory effects and structure activity relationships of Irish apple juice and Real Irish cider lipid bioactives against the platelet-activating factor (PAF)- and adenosine diphosphate (ADP)-related thrombotic and inflammatory manifestations in human platelets. Total Lipids (TL) were extracted from low, moderate and high in tannins apple juices and from their derived-through-fermentation cider products, as well as from commercial apple juice and cider. These were separated into neutral lipids (NL) and PL, while all lipid extracts were further assessed for their ability to inhibit aggregation of human platelets induced by PAF and ADP. In all cases, PL exhibited the strongest anti-platelet bioactivities and were further separated by high-performance liquid chromatography (HPLC) analysis into PL subclasses/fractions that were also assessed for their antiplatelet potency. The PL from low in tannins apple juice exhibited the strongest antiplatelet effects against PAF and ADP, while PL from its fermented cider product were less active. Moreover, the phosphatidylcholines (PC) in apple juices and the phosphatidylethanolamines (PE) in apple ciders were the most bioactive HPLC-derived PL subclasses against PAF-induced platelet aggregation. Structural elucidation of the fatty acid composition by gas chromatography mass spectra (GCMS) analysis showed that PL from all samples are rich in beneficial monounsaturated fatty acids (MUFA) and omega 3 (n-3) polyunsaturated fatty acids (PUFA), providing a possible explanation for their strong anti-platelet properties, while the favorable low levels of their omega-6/omega-3 (n-6/n-3) PUFA ratio, especially for the bioactive PC and PE subclasses, further support an anti-inflammatory cardio-protective potency for these apple products. In conclusion, Irish apple juice and Real Irish cider were found to possess bioactive PL compounds with strong antiplatelet and anti-inflammatory properties, while fermentation seems to be an important modulating factor on their lipid content, structures and bioactivities. However, further studies are needed to evaluate these effects.

Bioactive Lipids of Marine Microalga Chlorococcum sp. SABC 012504 with Anti-Inflammatory and Anti-Thrombotic Activities.

Microalgae are at the start of the food chain, and many are known producers of a significant amount of lipids with essential fatty acids. However, the bioactivity of microalgal lipids for anti-inflammatory and antithrombotic activities have rarely been investigated. Therefore, for a sustainable source of the above bioactive lipids, the present study was undertaken. The total lipids of microalga Chlorococcum sp., isolated from the Irish coast, were fractionated into neutral-, glyco-, and phospho-lipids, and were tested in vitro for their anti-inflammatory and antithrombotic activities. All tested lipid fractions showed strong anti-platelet-activating factor (PAF) and antithrombin activities in human platelets (half maximal inhibitory concentration (IC50) values ranging ~25-200 µg of lipid) with the highest activities in glyco- and phospho-lipid fractions. The structural analysis of the bioactive lipid fraction-2 revealed the presence of specific sulfoquinovosyl diacylglycerols (SQDG) bioactive molecules and the HexCer-t36:2 (t18:1/18:1 and 18:2/18:0) cerebrosides with a phytosphingosine (4-hydrosphinganine) base, while fraction-3 contained bioactive phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecules. These novel bioactive lipids of Chlorococcum sp. with putative health benefits may indicate that marine microalgae can be a sustainable alternative source for bioactive lipids production for food supplements and nutraceutical applications. However, further studies are required towards the commercial technology pathways development and biosafety analysis for the use of the microalga.

The effects of cooking salmon sous-vide on its antithrombotic properties, lipid profile and sensory characteristics.

Fish contains bioactive polar lipids (PL) and is mainly consumed cooked. The aim of this study was to evaluate the sensory characteristics of sous-vide cooked salmon and the in vitro cardio-protective properties of its PL. PL were extracted from brined and un-brined sous-vide preparations in 52 °C, 65 °C, and 80 °C, while their antithrombotic cardio-protective properties were assessed in human platelets and their fatty acid (FA) content was evaluated by LC-MS. Sensory tests were performed using napping followed by check-all-that apply (CATA). Mild temperatures (52 °C, 65 °C) did not affect the inhibitory effect of PL from brined and un-brined salmon, against human platelet aggregation induced by platelet-activating factor (PAF), thrombin, adenosine diphosphate (ADP) or collagen. In higher temperatures used for pasteurization (80 °C), a reduction of antithrombotic properties was observed in PL from both un-brined and brined salmon samples. This reduction was accompanied by a decrease of their n3 eicosapentaenoic acid (EPA) and overall polyunsaturated FA (PUFA) content, but only in the PL of the un-brined salmon preparations. Thus, changes in the fatty acid content of PL of all sous vide salmon preparations, and especially of specific PUFA, seem to be associated with the observed changes in their antithrombotic potency. Changes in the content of the n-3 docosapentaenoic acid (DPA), a precursor of EPA and docosahexaenoic acid (DHA), seem to be associated with differences observed in the antithrombotic potency of PL from different sous vide salmon preparations. Taste attributes were not affected by the conditions of sous-vide preparations, whereas slight textural differences were observed in samples treated at 65 °C and 80 °C. These outcomes, if combined with the observed low values of the n-6/n-3 PUFA ratio in PL of all sous-vide preparations, further suggest a beneficial role for such a mild cooking procedure for preserving the antithrombotic and cardio-protective properties of salmon without affecting its sensory characteristics.

Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: Potential role of antiplatelet agents.

Platelets are central to inflammation-related manifestations of cardiovascular diseases (CVD) such as atherosclerosis. Platelet-activating factor (PAF), thrombin, thromboxane A2 (TxA2), and adenosine diphosphate (ADP) are some of the key agonists of platelet activation that are at the intersection between a plethora of inflammatory pathways that modulate pro-inflammatory and coagulation processes. The aim of this article is to review the role of platelets and the relationship between their structure, function, and the interactions of their constituents in systemic inflammation and atherosclerosis. Antiplatelet therapies are discussed with a view to primary prevention of CVD by the clinical reduction of platelet reactivity and inflammation. Current antiplatelet therapies are effective in reducing cardiovascular risk but increase bleeding risk. Novel therapeutic antiplatelet approaches beyond current pharmacological modalities that do not increase the risk of bleeding require further investigation. There is potential for specifically designed nutraceuticals that may become safer alternatives to pharmacological antiplatelet agents for the primary prevention of CVD but there is serious concern over their efficacy and regulation, which requires considerably more research.

Thrombosis and COVID-19: The Potential Role of Nutrition.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease (COVID-19), is a contagion that has rapidly spread around the globe. COVID-19 has caused significant loss of life and disrupted global society at a level never before encountered. While the disease was predominantly characterized by respiratory symptoms initially, it became clear that other systems including the cardiovascular and neurological systems were also involved. Several thrombotic complications were reported including venous thrombosis, vasculitis, cardiomyopathy, and stroke. Thrombosis and inflammation are implicated in various non-communicable diseases (NCDs). This is of significant concern as people with pre-existing conditions such as cardiovascular disorders, renal disorders, obesity, metabolic syndrome, and diabetes are at greater risk of severe COVID-19 infection. Consequently, the research surrounding the use of anticoagulants, antiplatelet, and antithrombotic strategies for prophylaxis and treatment of COVID-19 is of critical importance. The adoption of a healthy diet, physical exercise, and lifestyle choices can reduce the risk factors associated with NCDs and the thrombo-inflammatory complications. In this review, these thrombotic complications and potential foods, nutraceuticals, and the antithrombotic constituents within that may prevent the onset of severe thrombotic complications as a result of infection are discussed. While nutrition is not a panacea to tackle COVID-19, it is apparent that a patient's nutritional status may affect patient outcomes. Further intensive research is warranted to reduce to incidence of thrombotic complications.

Comment on "Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients 2020, 12, 1181".

The novel coronavirus (COVID-19) pandemic, [...].

Structural Elucidation of Irish Ale Bioactive Polar Lipids with Antithrombotic Properties.

The structures of bioactive polar lipids (PLs) of Irish ale with potent antithrombotic and cardioprotective properties were elucidated. Ale PL was fractionated by preparative thin layer chromatography (TLC) into subclasses, and their antithrombotic effect was assessed against human platelet aggregation induced by the pro-inflammatory mediator, platelet-activating factor (PAF). The fatty acid content and the overall structures of ale PL were elucidated by liquid chromatography mass spectrometry (LC-MS). Phosphatidylcholines (PC) and molecules of the sphingomyelin (SM) family exhibited the strongest anti-PAF effects, followed by phosphatidylethanolamines (PE). PC contained higher amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and thus the lowest n-6/n-3 ratio. Bioactive diacyl and alkyl-acyl PC and PE molecules bearing n-3 PUFA at their sn-2 position, especially docosahexaenoic acid (DHA) and α-linolenic acid (ALA) but mostly oleic acid (OA), were identified in both PC and PE subclasses. Eicosapentaenoic acid (EPA) was present only in bioactive PC molecules and not in PE, explaining the lower anti-PAF effects of PE. Bioactive sphingolipid and glycolipid molecules with reported anti-inflammatory and anti-tumour properties, such as specific ceramides and glucosylcerebrosides with sphingosine, phytosphingosine and dihydrosphingosine bases but also specific monogalactodiglycerides and SM species bearing ALA at their sn-2 position, were identified in the SM subclass, providing a rational for its strong bioactivities against the PAF pathway. Further studies are required on the health benefits of bioactive PL from beer and brewery by-products.

Yoghurt fermentation alters the composition and antiplatelet properties of milk polar lipids.

Dairy polar lipids (PL) seem to exhibit antiplatelet effects. However, it is not known what molecular species may be responsible. In this study, we confirmed using C30 reversed-phase (C30RP) ultra-high-performance liquid chromatography (UHPLC) coupled to high resolution accurate mass tandem mass spectrometry (HRAM-MS/MS) that fermentation of yoghurts from ovine milk using specific starter cultures altered the PL composition. These lipid alterations occurred concomitant with increased antithrombotic properties of the yoghurts PL fractions against platelet-activating factor (PAF) and thrombin-induced platelet aggregation. Specifically, elevation in phosphatidylethanolamine (PE), sphingomyelin (SM), phosphatidylcholine (PC) and their molecular species were observed following yoghurt fermentation. Furthermore, PC(18:0/18:1), PE(18:1/18:2), SM(d18:0/22:0) and several other molecular species were significantly inversely correlated with the inhibition of PAF and thrombin. These molecular species were abundant in the most bioactive yoghurts fermented by S. thermophilus and L. acidophilus, which suggest that fermentation by these microorganisms increases the antithrombotic properties of ovine milk PL.