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The relevance of lifestyle, including diet and exercise, has been associated with improved learning and memory capacity, delayed age-related cognitive decline, and a reduced risk of neurodegeneration. Most neurodegenerative diseases are defined as complex multifactorial disorders in which genetic and environmental factors greatly contribute to their onset. Although inflammatory cells produce reactive oxygen species (ROS), oxidative stress itself might exert pro-inflammatory effects and an uncontrolled response could lead to a state of chronic inflammation. Anti-inflammatory dietary approaches unify the disciplines of nutrition, immunity, and neurology. Personalized dietary interventions will be developed based on an individual's genetic makeup, metabolic profile, and gut microbiota composition, thanks to advances in genomics, metabolomics, and microbiome research. The relevance of dietary patterns in decreasing inflammation relies on the role of specific antioxidant nutrients, which might contribute to a decrease in the levels of ROS. This review aims to summarize recent advancements in neuroscience and immunology that have revealed the crucial role that diet and the immune system play in brain function and disease progression. Nutrition influences the immune system, and in turn, the immune system impacts neurological health. This bidirectional relationship suggests that targeted nutritional interventions could modulate immune responses to delay or mitigate the progression of neurodegenerative diseases potentially. This approach focuses on the use of specific nutrients and dietary components that influence the immune system and inflammatory pathway. Key elements of immunonutrition include omega-3 fatty acids, antioxidants, vitamins and various bioactive compounds found in foods.

Parkinson's disease (PD) is the second most common neurodegenerative disease, with genetic factors like mutations in the LRRK2 gene being a key cause of late-onset autosomal dominant parkinsonism. Nutritional strategies, such as using bioactive peptides with anti-inflammatory properties from sources like hemp protein, are gaining interest as an alternative to pharmacological therapies. In this study, we used an LRRK2-associated PD mouse model to test the efficacy of a hempseed protein hydrolysate (HPH60A + 15F) with antioxidant and anti-inflammatory properties. Mice were given HPH60A + 15F (10 mg kg -1 day -1 ) orally for 7 days. After treatment, brain tissue and macrophages were analyzed to assess neuroinflammation markers. Additionally, the neuroavailable peptidome was characterized using an in vitro model simulating the intestinal and blood-brain barriers. The oral treatment has been shown to reduce protein aggregates of α-syn, CD68, iNOS, and COX2 in the brain. The treatment also significantly lowered TNF-α gene expression in the striatum, with a notable reduction in the gene expression of other pro-inflammatory cytokines in bone marrow-derived macrophages (BMDMs), such as IL-1β or IL-6. The peptide TVTAMNVVYALK was proposed as a potential highly active peptide, able to exert anti-inflammatory effects in the brain. The results have shown that HPH60A + 15F is capable of alleviating neuroinflammation by reducing the expression of pro-inflammatory cytokines, which could have promising effects in PD.

Extracellular vesicles (EVs) are lipid-bound membrane vesicles released from cells, containing active compounds, which can be found in different foods. In this review, the role of food-derived vesicles (FDVs) as immunomodulatory drivers is summarized, with a focus on sources, isolation techniques and yields, as well as bioavailability and potential health implications. In addition, gaps and perspectives detected in this research field have been highlighted. FDVs have been efficiently extracted from different sources, and differential ultracentrifugation seems to be the most adequate isolation technique, with yields ranging from 10 8 to 10 14 EV particles/mL. Animal studies show promising results in how these FDVs might regulate different pathways related to inflammation. Further investigation on the production of stable components in a cost-effective way, as well as human studies demonstrating safety and health-promoting properties, since scarce information has been reported until now, in the context of modulating the immune system are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Yellow mealworm (Tenebrio molitor) larvae are increasingly recognized as a potential source of bioactive peptides due to their high protein content. Antimicrobial peptides from sustainable sources are a research topic of interest. This study aims to characterize the peptidome of T. molitor flour and an Alcalase-derived hydrolysate, and to explore the potential presence of antimicrobial peptides using in silico analyses, including prediction tools, molecular docking and parameter correlations., Results: T. molitor protein was hydrolysed using Alcalase, resulting in a hydrolysate (TMH10A) with a 10% degree of hydrolysis. The peptidome was analysed using LC-TIMS-MS/MS, yielding over 6000 sequences. These sequences were filtered using the PeptideRanker tool, selecting the top 100 sequences with scores >0.8. Bioactivity predictions indicated that specific peptides, particularly WLNSKGGF and GFIPYEPFLKKMMA, showed significant antimicrobial potential, particularly against bacteria, fungi and viruses. Correlations were found between antifungal activity and physicochemical properties such as net charge, hydrophobicity and isoelectric point., Conclusions: The study identified specific T. molitor-derived peptides with strong predicted antimicrobial activity through in silico analysis. These peptides, particularly WLNSKGGF and GFIPYEPFLKKMMA, might offer potential applications in food safety and healthcare. Further experimental validation is required to confirm their efficacy. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

The link between diet and immune function is a growing area of interest, recognized not only by the scientific community but also by global health organizations, such as the World Health Organization (WHO) [...].

Pectin is a natural biopolymer, which can be extracted from food by-products, adding value to raw material, with a structure more complex than that of other polysaccharides. The gelling properties of these molecules, together with the bioactivity that these can exert, make them suitable to be used as ingredients and bioactive agents. In this review, the characterization of pectin (structure, sources, techno-functional, and biological properties), the extraction methods, and their use in the food industry (food packaging, as carriers, and as ingredients) are described. Different by-products can be used as substrates to extract pectin, enhancing a sustainable food system as described by the circular economy principles. Pectin is characterized for their techno-functional and biological properties, such as gelling and thickening properties or modulation of microbiota both in animals and humans. Such properties make these molecules suitable for a wide range of applications within the food chain, serving as packaging or carriers in foodstuff, or for direct use as functional ingredients as fiber. Overall, pectin has been shown to exert as promising components to be introduced in the food system, although further research on scaling-up the production process and feasibility has to be done., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Three protein hydrolysates from Tenebrio molitor were obtained by enzymatic hydrolysis employing two food-grade proteases (i.e. Alcalase and Flavourzyme), and a complete characterisation of their composition was done. The digestion-derived products were obtained using the INFOGEST protocol. In vitro antioxidant activity and anti-inflammatory activities were evaluated. Tenebrio molitor flour and the protein hydrolysates showed a high ability to scavenge the DPPH radical (EC 50 values from 0.30 to 0.87 mg/mL). The hydrolysate obtained with a combination of the two food-grade proteases could decrease the gene expression of pro-inflammatory genes after being digested. Furthermore, the peptidome was fully determined for the first time for T. molitor hydrolysates and digests, and 40 peptides were selected based on their bioactivity to be evaluated by in silico tools, including prediction tools and molecular docking. These results provide new perspectives on the use of edible insects as sustainable and not nutritionally disadvantageous food for human consumption., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly "naive" CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 β and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.

Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO's recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired t -test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (-54.0%), and TAG levels (-49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome., Competing Interests: The authors declare no conflicts of interest.

Many edible insect species are attracting the attention of the food industry and consumers in Western societies due to their high content and quality of protein, and consequently, the potential to be used as a more environmentally friendly dietary source could be beneficial for humans. On the other hand, prevention of inflammatory diseases using nutritional interventions is currently being proposed as a sustainable and cost-effective strategy to improve people's health. In this regard, finding bioactive compounds such as peptides with anti-inflammatory properties from sustainable sources ( e.g. , edible insects) is one area of particular interest, which might have a relevant role in immunonutrition. This review aims to summarize the recent literature on the discovery of immunomodulatory peptides through in vitro studies from edible insects, as well as to describe cell-based assays aiming to prove their bioactivity. On top of that, in vivo studies ( i.e. , animal and human), although scarce, have been mentioned in relation to the topic. In addition, the challenges and future perspectives related to edible-insect peptides and their role in immunonutrition are discussed. The amount of literature aiming to demonstrate the potential immunomodulatory activity of edible-insect peptides is scarce but promising. Different approaches have been employed, especially cell assays and animal studies employing insect meal as supplementation in the diet. Insects such as Tenebrio molitor or Gryllodes sigillatus are some of the most studied and have demonstrated to contain bioactive peptides. Further investigations, mostly with humans, are needed in order to clearly state that peptides from edible insects may contribute to the modulation of the immune system.

The incorporation of novel, functional, and sustainable foods in human diets is increasing because of their beneficial effects and environmental-friendly nature. Chia ( Salvia hispanica L.) has proved to be a suitable source of bioactive peptides via enzymatic hydrolysis. These peptides could be responsible for modulating several physiological processes if able to reach the target organ. The bioavailable peptides contained in a hydrolysate obtained with Alcalase, as functional foods, were identified using a transwell system with Caco-2 cell culture as the absorption model. Furthermore, 20 unique peptides with a molecular weight lower than 1000 Da and the higher statistical significance of the peptide-precursor spectrum match (-10 log P ) were assessed by in silico tools to suggest which peptides could be those exerting the demonstrated bioactivity. From the characterized peptides, considering the molecular features and the results obtained, the peptides AGDAHWTY, VDAHPIKAM, PNYHPNPR, and ALPPGAVHW are anticipated to be contributing to the antioxidant and/or ACE inhibitor activity of the chia protein hydrolysates.

Promoting dietary patterns in which the content of vegetables is higher than the current consumption of them is one of the strategies to achieve a sustainable food system while promoting health in humans. Hemp (Cannabis sativa L.) protein contains bioactive peptides that can be released via enzymatic hydrolysis. These peptides must reach the target organ in order to potentially exert bioactivity and regulate specific metabolic pathways. The peptides contained in two bioavailable hempseed protein hydrolysates (bioHPHs) showing anti-inflammatory activity were identified using a transwell system employing CACO-2 cell culture as absorption model and subjected to in silico analysis to select 10 unique peptides. These sequences were chemically synthetized to verify their activity in primary human monocytes (assessing gene expression of IL-1β, IL-6, TNF-α, IL-4, IL-10, and TLR4), in addition to evaluate the interaction with TRL4/MD2 by molecular docking. Six peptides (DDNPRRF, SRRFHLA, RNIFKGF, VREPVFSF, QADIFNPR and SAERGFLY) showed high immunomodulatory activity in in vitro and the mechanisms of interaction with TLR4/MD2 were described. Bioavailable anti-inflammatory hempseed-derived peptides were identified, and their activity verified, suggesting the health benefits that the ingestion of HPHs could exert in humans. These findings open new opportunities for developing nutritional strategies with hemp as a dietary source of biopeptides to prevent the development and progression of inflammatory-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Olea europaea L. is the source of virgin olive oil (VOO). During its extraction, a high amount of by-products (pomace, mill wastewaters, leaves, stones, and seeds) is originated, which possess an environmental problem. If the generation of waste cannot be prevented, its economic value must be recovered and its effects on the environment and climate change must be avoided or minimized. The bioactive compounds (e.g., phenols, pectins, peptides) of these by-product fractions are being investigated as nutraceutical due to the beneficial properties it might have. In this review, the aim is to summarize the in vivo studies carried out in animals and humans with bioactive compounds exclusively obtained from olive by-products, aiming to demonstrate the potential health benefits these products can exert, as well as to describe its use in the food industry as bioactive ingredient. Several food matrices have been fortified with olive by-products fractions, leading to an improvement of properties. Animal and human studies suggest the benefits of ingesting olive-derived products to promote health. However, the investigation until now is scarce and consequently, well-designed human studies are required in order to fully address and confirm the safety and health-promoting properties of olive oil by-products.

Malnutrition refers to a person's status as under- or overnourished, and it is usually associated with an inflammation status, which can subsequently imply a different health status, as the risk of infection is increased, along with a deterioration of the immune system. Children's immune systems are generally more susceptible to problems than adults. In the situation of malnutrition, because malnourished children's immune systems are compromised, they are more likely to die. However, little is known about the underlying mechanism of altered immune functioning and how it relates to starvation. Nutritional interventions have been reported as cost-effective strategies to prevent or treat the development of malnourishment, considering the link between food intake and health, especially in children, and also the susceptibility of this population to diseases and how their health status during childhood might affect their long-term physiological growth. The ingestion of specific nutrients (e.g., vitamins or oligoelements) has been reported to contribute to the proper functioning of children's immune systems. In this review, we aim to describe the basis of malnutrition and how this is linked to the immune system, considering the role of nutrients in the modulation of the immune system and the risk of infection that can occur in these situations in children, as well as to identify nutritional interventions to improve their health.

Hemp seeds have attracted the interest of the food industry recently, to be employed as functional food, considering their nutritional composition, highlighting the high content and quality of the proteins. In this study, ten hemp protein hydrolysates (HPHs) were obtained by enzymatic hydrolysis with two food-grade proteases from a hemp protein isolate and the inflammatory properties were evaluated in Caco-2 cell line. To this end, the gene expression and the release of proinflammatory and anti-inflammatory cytokines by Caco-2 cells stimulated with bacterial lipopolysaccharide and treated with HPHs at concentrations of 50 and 100 μg/mL were analyzed. The peptides contained in each HPH were identified and those with higher quality of the match in the spectrum were subjected to in silico analyses to determine which peptides were bioactive and contributing to the immunomodulatory activity of the hydrolysates. The results suggest that the immunomodulatory properties of these HPHs could have a beneficial effect at the level of the intestinal epithelium. The HPH20A and HPH60A + 15F exerted high immunomodulatory properties based on the cytokine levels release. The oligopeptides MAEKEGFEWVSF and GLHLPSYTNTPQLVYIVK were proposed as the most active ones. The potential of these peptides as nutraceuticals to prevent or pretreat intestinal inflammation is promising, though requires validation by in vivo assays., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is one of the most prevalent diseases in modern society, governed by both genetic and environmental factors, such as nutritional habits. This metabolic disorder is characterized by insulin resistance, which is related to high blood glucose levels, implying negative health effects in humans, hindering the healthy ageing of people. The relationship between food and health is clear, and the ingestion of specific nutrients modulates some physiological processes, potentially implying biologically relevant changes, which can translate into a health benefit. This review aims to summarize human studies published in which the purpose was to investigate the effect of protein ingestion (in native state or as hydrolysates) on human metabolism. Overall, several studies showed how protein ingestion might induce a decrease of glucose concentration in the postprandial state (area under the curve), although it is highly dependent on the source and the dose. Other studies showed no biological effects upon protein consumption, mostly with fish-derived products. In addition, the major challenges and perspectives in this research field are highlighted, suggesting the future directions, towards which scientists should focus on. The dietary intake of proteins has been proven to likely exert a beneficial effect on diabetes-related parameters, which can have a biological relevance in the prevention and pre-treatment of diabetes. However, the number of well-designed human studies carried out to date to demonstrate the effects of specific proteins or protein hydrolysates in vivo is still scarce.

Food supplements are products intended to complement the normal diet and consist of concentrated sources of nutrients or other substances with a nutritional or physiological effect. Although they are generally considered safe if the manufacturer's recommendations are followed, many of them have shown hepatotoxic properties. This can cause many diseases (e.g. steatohepatitis and cirrhosis) characterized by progressive damage and malfunction of the liver that in the long term can lead to death. A review of the literature was carried out to elucidate which dietary supplements have been associated with cases of hepatotoxicity in recent years, with emphasis on those relevant to the consumer and the new trends (e.g. cannabidiol). It has been reported that the supplements described as hepatotoxic are mainly of botanical origin (e.g. green tea or turmeric) and those used in sports (mainly anabolic androgenic steroids). There is a great variability of compounds described as causing liver damage, although sometimes it is not possible to identify them, because they are contaminants or adulterants of the products. In addition, the prevalence of toxic effects after the administration of supplements is difficult to define due to underreporting and the lack of specific studies. Globally regarding hepatotoxicity of dietary supplements, there is a paucity of well-conducted clinical trials on the efficacy of these compounds and the frequency of related liver damage, as the use of these products is largely uncontrolled.

Oleocanthal, OC, 2-(4-Hydroxyphenyl)ethyl(3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate, is a natural organic compound exclusively found in Olea europaea L. (Oleoaceae), such as extra virgin olive oil (EVOO). Chemically, it is considered a monophenolic secoiridoid, taking part of the validated antioxidants naturally occurring in some plant-based foods. In this review, the aim is to summarize the identity and characteristics of this molecule, where it can be obtained (isolation from the natural source or chemical synthesis), as well as the use as food component. Then, the bioavailability, safety and studies aiming to demonstrate the potential health benefits, including in vitro and in vivo animal and human studies were also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lupins are an interesting source of nutrients, part of the Fabaceae family. More specifically, narrow-leafed lupin (Lupinus angustifolius L.) is a legume, largely produced in Australia, which is used both for human food and animal fodder. There is a growing interest in plant proteins-derived products due to benefits for the ecosystem and lower production costs compared to traditional animal sources of protein. This review aimed to summarize major and minor chemical components in Lupinus angustifolius L., and potential health benefits of this plant and product thereof. In particular, the protein fraction of Lupinus and their biological properties are described. L. angustifolius seed and proteins by-products can be used as a valuable source of high value-added compounds for diverse food products with the goal to maximize its economic value., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The immune system is somehow related to all the metabolic pathways, in a bidirectional way, and the nutritional interventions affecting these pathways might have a relevant impact on the inflammatory status of the individuals. Food-derived peptides have been demonstrated to exert several bioactivities by in vitro or animal studies. Their potential to be used as functional food is promising, considering the simplicity of their production and the high value of the products obtained. However, the number of human studies performed until now to demonstrate effects in vivo is still scarce. Several factors must be taken into consideration to carry out a high-quality human study to demonstrate immunomodulatory-promoting properties of a test item. This review aims to summarize the recent human studies published in which the purpose was to demonstrate bioactivity of protein hydrolysates, highlighting the main results and the limitations that can restrict the relevance of the studies. Results collected are promising, although in some studies, physiological changes could not be observed. When responses were observed, they sometimes did not refer to relevant parameters and the immunomodulatory properties could not be clearly established with the current evidence. Well-designed clinical trials are needed in order to evaluate the role of protein hydrolysates in immunonutrition.

New challenges in food production and processing are appearing due to increasing global population and the purpose of achieving a sustainable food system. Bioactive peptides obtained from food proteins can be employed to prevent or pre-treat several diseases such as diabetes, cardiovascular diseases, inflammation, thrombosis, cancer, etc. Research on the bioactivity of protein hydrolysates is very extensive, especially in vitro tests, although there are also tests in animal models and in humans studies designed to verify their efficacy. However, there is very little published literature on the functionality of these protein hydrolysates as an ingredient in food matrices, as well as the effect that thermal or non-thermal processing, and storage may have on the bioactivity of these bioactive peptides. This review aims to summarize the published literature on protein hydrolysates as a functional ingredient including processing, storage and simulated gastrointestinal digestion regarding the bioactivity of these peptides inside food matrices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The defense mechanism against harmful stimuli is inflammation. Indeed, neurodegenerative disorders can arise as a result of a persistent neuroinflammation. Beta-amyloid (Aβ 1-42 ) is an early trigger in the origination of Alzheimer's disease, leading to synaptic and cognitive impairments. Virgin olive oil (VOO) is correlated with a decreased risk of developing immune-inflammatory disorders, but the potential effects of the phenolic fraction (PF) from VOO in the modulation of neuroinflammatory processes in neutrophils remain unknown. In this study, we investigated the ability of the PF to modulate the activation of Aβ 1-42 -stimulated primary human neutrophils, focusing on the expression of gene and surface markers and the release of pro-inflammatory and chemoattractant mediators. Down-regulation of pro-inflammatory cytokine gene expression in Aβ 1-42 -treated neutrophils, among other changes, was reported. Furthermore, pretreatment with PF prevented neutrophil activation. The beneficial effects in the modulation of inflammatory responses show the relevance of VOO to achieve a healthier diet that can help prevent inflammatory diseases.

A prolonged inflammatory response can lead to the development of neurodegenerative diseases such as Alzheimer's disease. Enzymatic hydrolysis is a sustainable way to increase the value of protein sources by obtaining peptides that can exert bioactivity. Hemp ( Cannabis sativa L.) protein hydrolysates have been proven to exert anti-inflammatory activity. In this study, two hemp protein hydrolysate (HPHs), obtained with Alcalase as sole catalyst, or with Alcalase followed by Flavourzyme, were evaluated as inflammatory mediators (TNFα, IL-1β, IL-6, and IL-10), microglial polarization markers ( Ccr7 , iNos , Arg1 , and Ym1 ), and genes related to inflammasome activation ( Nlrp3 , Asc , Casp1 , and Il18 ), employing the lipopolysaccharide (LPS)-induced neuroinflammation model in murine BV-2 microglial cells. A significant decrease of the expression of proinflammatory genes (e.g., Tnfα , Ccr7 , inos , and Nlrp3 , among others) and increase of the expression anti-inflammatory cytokines in microglial cells was observed after treatment with the test HPHs. This result in the cell model suggests a polarization toward an anti-inflammatory M2 phenotype. Our results show that the evaluated HPHs show potential neuroprotective activity in microglial cells via the inflammasome.

The increase in the world population along with new policies aimed at a more sustainable world has led to the need of searching for new food sources, which are environmentally friendly, implying healthy and nutritious diets. This study explored the biological activity of two kiwicha ( Amaranthus caudatus L.) protein hydrolysates obtained with the aid of Bioprotease LA-660 regarding their anti-inflammatory response at the intestinal level, employing the CACO-2 cell line. The results obtained showed that the in vitro administration of these hydrolysates decreased the expression of proinflammatory cytokines, increased the expression of anti-inflammatory cytokines, and decreased the gene expression of the major components of inflammasomes in the intestinal CACO-2 cell model. To the best of our knowledge, this is the first study involving the evaluation of the anti-inflammatory activity of kiwicha hydrolysates at the intestinal level, employing the CACO-2 cell model and its ultrastructural characterization using scanning electron microscopy. We conclude that the Amaranthus caudatus hydrolysates are a valuable source of active peptides that take part as functional ingredients in food and nutraceutical preparations.

Vegetable proteins are appearing as a sustainable source for human consumption. Food-derived peptides are an important field of research in terms of bioactive molecules. In this study, seven vegetable proteins were enzymatically hydrolysed following an optimised treatment (sequential hydrolysis with subtilisin-trypsin-flavourzyme) to obtain dipeptidyl peptidase IV (DPP-IV) inhibitory peptides. Hydrolysates were fractionated by size exclusion chromatography and, from the most bioactive fractions (corresponding to Glycine max, Chenopodium quinoa and Lupinus albus proteins); peptides responsible for this bioactivity were identified by mass spectrometry. Peptides with adequate molecular features and based on in silico analysis were proposed as DPP-IV inhibitors from soy (EPAAV) lupine (NPLL), and quinoa (APFTVV). These vegetable protein sources are adequate to obtain protein hydrolysates for functional food., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The exponential increase in world population is leading to a need for new sustainable protein sources that could supply the high demands without resulting in an enormous environmental impact. Bioactive peptides from food proteins are currently seen as capable of modulating physiological processes, such as diabetes. The potential of insects as a cheap source of antidiabetic peptides is a recent research topic. In this work, fractionation and identification of dipeptidyl peptidase IV (DPP-IV) and α-glucosidase inhibitory peptides from mealworm (Tenebrio molitor) was carried out. Peptides from 500 to 1600 Da showed the highest level of DPP-IV inhibition (IC 50 value of 0.91 mg ml -1 ) and peptides below 500 Da showed the highest level of α-glucosidase inhibition (IC 50 value of 2.58 mg ml -1 ). Numerous novel peptides were identified from the most bioactive fractions, and based on the molecular features usually described for these peptides, some of them are suggested to be the bioactive peptides responsible for the inhibition observed (e.g. APVAH for DPP-IV inhibition and CSR for α-glucosidase inhibition). Hence, these insect protein hydrolysates or their purified fractions could be used as ingredients for regulation of the glycaemic index.

Protein hydrolysates bioactivity makes them suitable for functional food ingredients. However, their chemical reactivity with different molecules, mainly reducing sugars, might lead to a modification of their structure, and thus function, after their inclusion into food matrices. The effect of food matrix and the storage time on the antihypertensive and antioxidant capacity of sardine hydrolysates was evaluated. Furthermore, bioactivity remaining after simulated gastrointestinal digested samples was also analyzed to verify its potential to be administrated orally. Sugar containing matrix improved the ACE inhibitory and DPPH radical scavenging activity of hydrolysates after thermal treatment and storage up to 80%. Maillard reaction products were responsible for the changes observed in the bioactivity of enriched food. Digested samples showed different but still adequate bioactivity depending on the matrix containing the hydrolysate. These results support the potential of fish protein hydrolysates to be used as ingredient in food formulation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Production of bioactive peptides via enzymatic hydrolysis is a sustainable way to take advantage of proteinaceous by-products from food industry, such as fish discards. Sardine pilchardus protein was subjected to different enzymatic treatments using two endopeptidases of different selectivity and one exopeptidase in order to produce hydrolysates with antidiabetic activity. The highest dipeptidyl peptidase IV inhibitory activity was obtained by the combination of three enzymes (subtilisin, trypsin and flavourzyme) employed sequentially. This hydrolysate was subsequently purified by size exclusion chromatography to obtain fractions sorted by size (hydrodynamic volume). Peptides below 1400 Dalton had the highest activity, and these pools were analysed by mass spectrometry in order to identify the peptides responsible for that activity. Numerous peptides with adequate molecular features, it is, owning an alanine (A) as their penultimate N-terminal residue (e.g. NAPNPR, YACSVR) were identified and are proposed to be antidiabetic peptides from Sardine pilchardus muscle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bioactive peptides released from the enzymatic hydrolysis of food proteins are currently a trending topic in the scientific community. Their potential as antidiabetic agents, by regulating the glycemic index, and thus to be employed in food formulation, is one of the most important functions of these peptides. In this review, we aimed to summarize the whole process that must be considered when talking about including these molecules as a bioactive ingredient. In this regard, at first, the production, purification and identification of bioactive peptides is summed up. The detailed metabolic pathways described included carbohydrate hydrolases (glucosidase and amylase) and dipeptidyl-peptidase IV inhibition, due to their importance in the food-derived peptides research field. Then, their characterization, concerning bioavailability in vitro and in situ, stability and functionality in food matrices, and ultimately, the in vivo evidence (from invertebrate animals to humans), was described. The future applicability that these molecules have due to their biological potential as functional ingredients makes them an important field of research, which could help the world population avoid suffering from several diseases, such as diabetes.

The increasing world population has led to the need to search for new protein sources, such as insects, the harvesting of which can be economical and environmentally sustainable. This study explores the biological activities (angiotensin-converting enzyme (ACE) inhibition, antioxidant capacity, and dipeptidyl peptidase IV (DPP-IV) inhibition) of Tenebrio molitor hydrolysates produced by a set of food-grade proteases, namely subtilisin, trypsin, ficin and flavourzyme, and the degree of hydrolysis (DH), ranging from 5% to 20%. Trypsin hydrolysates exhibited the highest ACE inhibitory activity at a DH of 10% (IC 50 0.27 mg mL -1 ) in the experimental series, which was attributed to the release of short peptides containing Arg or Lys residues in the C terminus, and described as the ACE-inhibition feature. The levels of in vitro antioxidant activities were comparable to those reported for insect species. Subtilisin and trypsin hydrolysates at a DH of 10% displayed optimal DPPH scavenging and ferric reducing activities, which was attributed to the presence of 5-10-residue active peptides, as reported in the literature. Iron chelating activity was significantly favoured by increasing the DH, attaining a minimal IC 50 of 0.8 mg mL -1 at a DH of 20% regardless of the enzymatic treatment. Similarly, in vitro antidiabetic activity was significantly improved by extensive hydrolysis, and, more specifically, the presence of di- and tripeptides. In this regard, the combined treatment of subtilisin-flavourzyme at a DH of 20% showed maximal DPP-IV inhibition (IC 50 2.62 mg mL -1 ). To our knowledge, this is the first study evaluating the DPP-IV activity of Tenebrio molitor hydrolysates obtained from these commercial proteases. We conclude that Tenebrio molitor hydrolysates produced with food-grade proteases are a valuable source of active peptides that can be used as functional ingredients in food and nutraceutical preparations.