In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is regarded as a fatal neurodegenerative disease that is featured by progressive damage of the upper and lower motor neurons. To date, over 45 genes have been found to be connected with ALS pathology. The aim of this work was to computationally identify unique sets of protein hydrolysate peptides that could serve as therapeutic agents against ALS. Computational methods which include target prediction, protein-protein interaction, and peptide-protein molecular docking were used. The results showed that the network of critical ALS-associated genes consists of ATG16L2, SCFD1, VAC15, VEGFA, KEAP1, KIF5A, FIG4, TUBA4A, SIGMAR1, SETX, ANXA11, HNRNPL, NEK1, C9orf72, VCP, RPSA, ATP5B, and SOD1 together with predicted kinases such as AKT1, CDK4, DNAPK, MAPK14, and ERK2 in addition to transcription factors such as MYC, RELA, ZMIZ1, EGR1, TRIM28, and FOXA2. The identified molecular targets of the peptides that support multi-metabolic components in ALS pathogenesis include cyclooxygenase-2, angiotensin I-converting enzyme, dipeptidyl peptidase IV, X-linked inhibitor of apoptosis protein 3, and endothelin receptor ET-A. Overall, the results showed that AGL, APL, AVK, IIW, PVI, and VAY peptides are promising candidates for further study. Future work would be needed to validate the therapeutic properties of these hydrolysate peptides by in vitro and in vivo approaches.

Changes in Polar Lipid Composition in Balsam Fir during Seasonal Cold Acclimation and Relationship to Needle Abscission.

Needle abscission in balsam fir has been linked to both cold acclimation and changes in lipid composition. The overall objective of this research is to uncover lipid changes in balsam fir during cold acclimation and link those changes with postharvest abscission. Branches were collected monthly from September to December and were assessed for cold tolerance via membrane leakage and chlorophyll fluorescence changes at -5, -15, -25, -35, and -45 °C. Lipids were extracted and analyzed using mass spectrometry while postharvest needle abscission was determined gravimetrically. Cold tolerance and needle retention each significantly (p < 0.001) improved throughout autumn in balsam fir. There were concurrent increases in DGDG, PC, PG, PE, and PA throughout autumn as well as a decrease in MGDG. Those same lipids were strongly related to cold tolerance, though MGDG had the strongest relationship (R2 = 55.0% and 42.7% from membrane injury and chlorophyll fluorescence, respectively). There was a similar, albeit weaker, relationship between MGDG:DGDG and needle retention (R2 = 24.3%). Generally, a decrease in MGDG:DGDG ratio resulted in better cold tolerance and higher needle retention in balsam fir, possibly due to increased membrane stability. This study confirms the degree of cold acclimation in Nova Scotian balsam fir and presents practical significance to industry by identifying the timing of peak needle retention. It is suggested that MGDG:DGDG might be a beneficial tool for screening balsam fir genotypes with higher needle retention characteristics.

Buckwheat proteins: functionality, safety, bioactivity, and prospects as alternative plant-based proteins in the food industry.

The need for protein in human nutrition is rapidly increasing because of the increasing world population and consumer preference for high-protein foods. Plant proteins are gaining attention as sustainable means of meeting the global protein need due to their lower carbon footprint. Nonetheless, the food industry has neglected or underutilized many plant proteins, including buckwheat protein. Buckwheat is a pseudocereal and its groats contain beneficial components such as proteins, dietary fiber, vitamins, and bioactive polyphenols. The protein quality of buckwheat seeds varies between the tartary and common buckwheat types; both are gluten-free and contain considerable amount of indispensable amino acids. This review provides a detailed discussion on the profile, amino acid composition, digestibility, allergenicity, functional properties, and bioactivity of buckwheat proteins. Prospects of processing buckwheat for improving protein digestibility and deactivating allergenic epitopes were also discussed. Based on the literature, buckwheat protein has a tremendous potential for utilization in structuring food products and developing peptide-based functional foods for disease prevention. Future research should develop new processing technologies for further improvement of the quality and functional properties of buckwheat protein in order to facilitate its utilization as an alternative plant-based protein toward meeting the global protein supply.

Sialic acid-based strategies for the prevention and treatment of Helicobacter pylori infection: Emerging trends in food industry.

Approximately 50% of the world population is infected with Helicobacter pylori. Antibiotics are widely used for H. pylori infection treatment but there are drawbacks, e.g., the emergence of antibiotic-resistant bacteria. Sialic acids are a family of acylated derivatives of a nine-carbon carboxylated monosaccharide. Because sialic acid of the host cells is vital to H. pylori pathogenesis, sialic acid-guided therapies have been proposed for the prevention and treatment of H. pylori infection, including anti-adhesive therapy and site-specific delivery. This review aims to shed light on the prospects of sialic acid-based strategies in the food industry for developing functional foods with potent anti-H. pylori activity. In this work, progress on the identification of sialic acid-containing components as anti-adhesive agents against H. pylori is reviewed. The current applications of sialic acid-based delivery systems in eradicating H. pylori are discussed, including microspheres, beads, hydrogels, and nanoparticles. The challenges and future perspectives of sialic acid-guided strategies and the possibility of their applications in food industry are highlighted. Antibiotic resistance is still a major challenge and the sialic acid-based technologies have tremendous potential to be utilized to develop functional foods that hold promise to be a future trend for preventing or treating H. pylori infection.

Preparation, pungency and bioactivity of gingerols from ginger (Zingiber officinale Roscoe): a review.

Ginger has been widely used for different purposes, such as condiment, functional food, drugs, and cosmetics. Gingerols, the main pungent component in ginger, possess a variety of bioactivities. To fully understand the significance of gingerols in the food and pharmaceutical industry, this paper first recaps the composition and physiochemical properties of gingerols, and the major extraction and synthesis methods. Furthermore, the pungency and bioactivity of gingerols are reviewed. In addition, the food application of gingerols and future perspectives are discussed. Gingerols, characterized by a 3-methoxy-4-hydroxyphenyl moiety, are divided into gingerols, shogaols, paradols, zingerone, gingerdiones and gingerdiols. At present, gingerols are extracted by conventional, innovative, and integrated extraction methods, and synthesized by chemical, biological and in vitro cell synthesis methods. Gingerols can activate transient receptor potential vanilloid type 1 (TRPV1) and induce signal transduction, thereby exhibiting its pungent properties and bioactivity. By targeted mediation of various cell signaling pathways, gingerols display potential anticancer, antibacterial, blood glucose regulatory, hepato- and renal-protective, gastrointestinal regulatory, nerve regulatory, and cardiovascular protective effects. This review contributes to the application of gingerols as functional ingredients in the food and pharmaceutical industry.

Disaggregation of Islet Amyloid Polypeptide Fibrils as a Potential Anti-Fibrillation Mechanism of Tetrapeptide TNGQ.

Islet amyloid polypeptide (IAPP) fibrillation has been commonly associated with the exacerbation of type 2 diabetes prognosis. Consequently, inhibition of IAPP fibrillation to minimize ß-cell cytotoxicity is an important approach towards ß-cell preservation and type 2 diabetes management. In this study, we identified three tetrapeptides, TNGQ, MANT, and YMSV, that inhibited IAPP fibrillation. Using thioflavin T (ThT) fluorescence assay, circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and molecular docking, we evaluated the potential anti-fibrillation mechanism of the tetrapeptides. ThT fluorescence kinetics and microscopy as well as transmission electron microscopy showed that TNGQ was the most effective inhibitor based on the absence of normal IAPP fibrillar morphology. CD spectroscopy showed that TNGQ maintained the α-helical conformation of monomeric IAPP, while DLS confirmed the presence of varying fibrillation species. Molecular docking showed that TNGQ and MANT interact with monomeric IAPP mainly by hydrogen bonding and electrostatic interaction, with TNGQ binding at IAPP surface compared to YMSV, which had the highest docking score, but interact mainly through hydrophobic interaction in IAPP core. The highly polar TNGQ was the most active and appeared to inhibit IAPP fibrillation by disaggregation of preformed IAPP fibrils. These findings indicate the potential of TNGQ in the development of peptide-based anti-fibrillation and antidiabetic nutraceuticals.

Curcumin-Induced Stabilization of Protein-Based Nano-Delivery Vehicles Reduces Disruption of Zwitterionic Giant Unilamellar Vesicles.

Curcumin-loaded native and succinylated pea protein nanoparticles, as well as zwitterionic giant unilamellar vesicles were used in this study as model bioactive compound loaded-nanoparticles and biomembranes, respectively, to assess bio-nano interactions. Curcumin-loaded native protein-chitosan and succinylated protein-chitosan complexes, as well as native protein-chitosan and succinylated protein-chitosan hollow, induced leakage of the calcein encapsulated in the giant unilamellar vesicles. The leakage was more pronounced with hollow protein-chitosan complexes. However, curcumin-loaded native protein and curcumin-loaded succinylated protein nanoparticles induced calcein fluorescence quenching. Dynamic light scattering measurements showed that the interaction of curcumin-loaded native protein, curcumin-loaded succinylated protein, native protein-chitosan, and succinylated protein-chitosan complexes with the giant unilamellar vesicles caused a major reduction in the size of the lipid vesicles. Confocal and widefield fluorescence microscopy showed rupturing of the unilamellar vesicles after treatment with native pea protein-chitosan and succinylated pea protein-chitosan complexes. The nature of interaction between the curcumin-loaded protein nanoparticles and the biomembranes, at the bio-nano interface, is influenced by the encapsulated curcumin. Findings from this study showed that, as the protein plays a crucial role in stabilizing the bioactive compound from chemical and photodegradation, the encapsulated nutraceutical stabilizes the protein nanoparticle to reduce its interaction with biomembranes.

TNKPVI, a Putative Bioaccessible Pharmacophore of Anti-Inflammatory Potato Patatin-Derived Decapeptide DIKTNKPVIF.

Potato protein-derived decapeptide DIKTNKPVIF exerted anti-inflammatory activity in animal models when delivered via intragastric gavage and intraperitoneal injection. However, DIKTNKPVIF is susceptible to hydrolysis in the digestive tract, which will decrease its bioaccessibility and possibly bioactivity. In this study, the anti-inflammatory activity of fragments generated from in silico gastrointestinal enzymatic hydrolysis of DIKTNKPVIF was investigated using the human monocytic (THP-1) cell line. The simulated digestion by pepsin and trypsin released four fragments, DIKTNKPVI, TNKPVIF, DIK and TNKPVI. The peptides lacked the cleavage sites of chymotrypsin. All five peptides were predicted to be non-toxic, which was validated using cytotoxicity assay at 0.25-1 mM peptide concentration. However, the peptides were predicted to possess poor pharmacokinetic profiles, including low passive gastrointestinal absorption and blood-brain barrier permeability. TNKPVIF, DIK and TNKPVI significantly reduced the amount of pro-inflammatory interleukin (IL)-6, IL-8 and tumor necrosis factor in lipopolysaccharide-activated THP-1 cells. Notably, the anti-inflammatory activity of fragment TNKPVI was comparable to that of the parent decapeptide while peptide fragment DIKTNKPVI had no apparent effect on the pro-inflammatory cytokines. This highlights the important role of the C-terminal phenylalanine residue of the parent peptide in the bioactivity. Furthermore, given its activity and the absence of cleavage sites of major digestive proteases, TNKPVI could be the biostable and bioaccessible pharmacophore of potato patatin-derived anti-inflammatory decapeptide DIKTNKPVIF.

A Concise Review of Current In Vitro Chemical and Cell-Based Antioxidant Assay Methods.

Antioxidants remain interesting molecules of choice for suppression of the toxic effects of free radicals in foods and human systems. The current practice involves the use of mainly synthetic molecules as potent antioxidant agents. However, due to the potential negative impact on human health, there is an intensive effort within the research community to develop natural alternatives with similar antioxidant efficacy but without the negative side effects of synthetic molecules. Still, the successful development of new molecules depends on the use of reliable chemical or cell culture assays to screen antioxidant properties. Chemical antioxidant assays include the determination of scavenging ability against free radicals such as DPPH, superoxide anion radicals, hydroxyl radicals, hydrogen peroxide, and nitric oxide. Other antioxidant tests include the ability of compounds to bind and sequester prooxidant metal cations, reduce ferric iron, and attenuate the rate of lipid oxidation. Ex vivo tests utilize cell cultures to confirm entry of the molecules into cells and the ability to quench synthetic intracellular free radicals or to stimulate the increased biosynthesis of endogenous antioxidants. In order to assist researchers in their choice of antioxidant evaluation methods, this review presents background scientific information on some of the most commonly used antioxidant assays with a comparative discussion of the relevance of published literature data to food science and human nutrition applications.

Zanthoxylum Species: A Comprehensive Review of Traditional Uses, Phytochemistry, Pharmacological and Nutraceutical Applications.

Zanthoxylum species (Syn. Fagara species) of the Rutaceae family are widely used in many countries as food and in trado-medicinal practice due to their wide geographical distribution and medicinal properties. Peer reviewed journal articles and ethnobotanical records that reported the traditional knowledge, phytoconstituents, biological activities and toxicological profiles of Z. species with a focus on metabolic and neuronal health were reviewed. It was observed that many of the plant species are used as food ingredients and in treating inflammation, pain, hypertension and brain diseases. Over 500 compounds have been isolated from Z. species, and the biological activities of both the plant extracts and their phytoconstituents, including their mechanisms of action, are discussed. The phytochemicals responsible for the biological activities of some of the species are yet to be identified. Similarly, biological activities of some isolated compounds remain unknown. Taken together, the Z. species extracts and compounds possess promising biological activities and should be further explored as potential sources of new nutraceuticals and drugs.

Effects of high power ultrasound on the enzymolysis and structures of sweet potato starch.

BACKGROUND: The general enzymatic method for producing reducing sugar is liquefaction followed by saccharification of starch. This method results in lower yields, consuming high energy and time. Therefore, the present study evaluated a new approach for producing reducing sugar from sweet potato starch (SPS), including simultaneous liquefaction (by α-amylase) and saccharification (by glucoamylase) of SPS pretreated with high power ultrasound. The effects of ultrasound parameters on the conversion rate of SPS and mechanism were investigated. RESULTS: The optimum ultrasound pretreatment conditions were a frequency of 20 kHz, SPS concentration of 125 g L-1 , temperature of 30 °C, pulsed on-time of 3 s, pulsed off-time of 5 s, power density of 8 W mL-1 and sonication time of 15 min. The ultrasound assisted enzymolysis resulted in a SPS conversion rate of 59.10%, which was improved by 56.35% compared to the control. The results of pasting properties and thermal analysis showed that ultrasound pretreatment decreased the peak viscosity, breakdown temperature, setback viscosity, gelatinization range (TC - TO ) and enthalpy of gelatinization (ΔH) of SPS significantly (P < 0.05) by 12.1%, 7.6%, 6.6%, 18.8% and 44.4%, respectively. Fourier-transform infrared spectroscopy indicated that ultrasound damaged the ordered structures and crystallization zone. This was confirmed by X-ray diffraction analysis, which showed that the relative crystallinity was reduced by 15.0%. Scanning electron microscopy showed that ultrasound destroyed the surfaces and the linkages between starch granules. CONCLUSION: Prior to simultaneous liquefaction and saccharification of SPS, high power ultrasound pretreatment is a promising method for improving the conversion rate of starch. © 2020 Society of Chemical Industry.

Bioinformatics and peptidomics approaches to the discovery and analysis of food-derived bioactive peptides.

There are emerging advancements in the strategies used for the discovery and development of food-derived bioactive peptides because of their multiple food and health applications. Bioinformatics and peptidomics are two computational and analytical techniques that have the potential to speed up the development of bioactive peptides from bench to market. Structure-activity relationships observed in peptides form the basis for bioinformatics and in silico prediction of bioactive sequences encrypted in food proteins. Peptidomics, on the other hand, relies on "hyphenated" (liquid chromatography-mass spectrometry-based) techniques for the detection, profiling, and quantitation of peptides. Together, bioinformatics and peptidomics approaches provide a low-cost and effective means of predicting, profiling, and screening bioactive protein hydrolysates and peptides from food. This article discuses the basis, strengths, and limitations of bioinformatics and peptidomics approaches currently used for the discovery and analysis of food-derived bioactive peptides.

Prospects in the use of aptamers for characterizing the structure and stability of bioactive proteins and peptides in food.

Food-derived bioactive proteins and peptides have gained acceptance among researchers, food manufacturers and consumers as health-enhancing functional food components that also serve as natural alternatives for disease prevention and/or management. Bioactivity in food proteins and peptides is determined by their conformations and binding characteristics, which in turn depend on their primary and secondary structures. To maintain their bioactivities, the molecular integrity of bioactive peptides must remain intact, and this warrants the study of peptide form and structure, ideally with robust, highly specific and sensitive techniques. Short single-stranded nucleic acids (i.e. aptamers) are known to have high affinity for cognate targets such as proteins and peptides. Aptamers can be produced cost-effectively and chemically derivatized to increase their stability and shelf life. Their improved binding characteristics and minimal modification of the target molecular signature suggests their suitability for real-time detection of conformational changes in both proteins and peptides. This review discusses the developmental progress of systematic evolution of ligands by exponential enrichment (SELEX), an iterative technology for generating cost-effective aptamers with low dissociation constants (K d) for monitoring the form and structure of bioactive proteins and peptides. The review also presents case studies of this technique in monitoring the structural stability of bioactive peptide formulations to encourage applications in functional foods. The challenges and potential of aptamers in this research field are also discussed. Graphical abstract Advancing bioactive proteins and peptide functionality via aptameric ligands.

The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions.

Animal and human clinical studies have demonstrated the ability of dietary food proteins to modulate endogenous lipid levels during abnormal lipid metabolism (dyslipidemia). Considering the susceptibility of proteins to gastric proteolytic activities, the hypolipidemic functions of proteins are possibly due, in part, to their peptide fragments. Food-derived peptides may directly modulate abnormal lipid metabolism in cell cultures and animal models of dyslipidemia. The peptides are thought to act by perturbing intestinal absorption of dietary cholesterol and enterohepatic bile acid circulation, and by inhibiting lipogenic enzymatic activities and gene expression in hepatocytes and adipocytes. Recent evidence indicates that the hypolipidemic activities of some peptides are due to activation of hepatic lipogenic transcription factors. However, detailed molecular mechanisms and structural requirements of peptides for these activities are yet to be elucidated. As hypolipidemic peptides can be released during enzymatic food processing, future studies can explore the prospects of combating metabolic syndrome and associated complications using peptide-rich functional food and nutraceutical products.

Microalgae Proteins as Sustainable Ingredients in Novel Foods: Recent Developments and Challenges.

Microalgae are receiving increased attention in the food sector as a sustainable ingredient due to their high protein content and nutritional value. They contain up to 70% proteins with the presence of all 20 essential amino acids, thus fulfilling human dietary requirements. Microalgae are considered sustainable and environmentally friendly compared to traditional protein sources as they require less land and a reduced amount of water for cultivation. Although microalgae's potential in nutritional quality and functional properties is well documented, no reviews have considered an in-depth analysis of the pros and cons of their addition to foods. The present work discusses recent findings on microalgae with respect to their protein content and nutritional quality, placing a special focus on formulated food products containing microalgae proteins. Several challenges are encountered in the production, processing, and commercialization of foods containing microalgae proteins. Solutions presented in recent studies highlight the future research and directions necessary to provide solutions for consumer acceptability of microalgae proteins and derived products.

Molecular Mechanistic Insights into Dipeptidyl Peptidase-IV Inhibitory Peptides to Decipher the Structural Basis of Activity.

Dipeptidyl peptidase-IV (DPP-IV) inhibiting peptides have attracted increased attention because of their possible beneficial effects on glycemic homeostasis. However, the structural basis underpinning their activities has not been well understood. This study combined computational and in vitro investigations to explore the structural basis of DPP-IV inhibitory peptides. We first superimposed the Xaa-Pro-type peptide-like structures from several crystal structures of DPP-IV ligand-protein complexes to analyze the recognition interactions of DPP-IV to peptides. Thereafter, a small set of Xaa-Pro-type peptides was designed to explore the effect of key interactions on inhibitory activity. The intramolecular interaction of Xaa-Pro-type peptides at the first and third positions from the N-terminus was pivotal to their inhibitory activities. Residue interactions between DPP-IV and residues of the peptides at the fourth and fifth positions of the N-terminus contributed significantly to the inhibitory effect of Xaa-Pro-type tetrapeptides and pentapeptides. Based on the interaction descriptors, quantitative structure-activity relationship (QSAR) studies with the DPP-IV inhibitory peptides resulted in valid models with high R2 values (0.90 for tripeptides; 0.91 for tetrapeptides and pentapeptides) and Q2 values (0.33 for tripeptides; 0.68 for tetrapeptides and pentapeptides). Taken together, the structural information on DPP-IV and peptides in this study facilitated the development of novel DPP-IV inhibitory peptides.

Self-Assembled Food Peptides: Recent Advances and Perspectives in Food and Health Applications.

Self-assembling peptides are rapidly gaining attention as novel biomaterials for food and biomedical applications. Peptides self-assemble when triggered by physical or chemical factors due to their versatile physicochemical characteristics. Peptide self-assembly, when combined with the health-promoting bioactivity of peptides, can also result in a plethora of biofunctionalities of the biomaterials. This perspective highlights current developments in the use of food-derived self-assembling peptides as biomaterials, bioactive nutraceuticals, and potential dual functioning bioactive biomaterials. Also discussed are the challenges and opportunities in the use of self-assembling bioactive peptides in designing biocompatible, biostable, and bioavailable multipurpose biomaterials.

Screening, separation and identification of metal-chelating peptides for nutritional, cosmetics and pharmaceutical applications.

Metal-chelating peptides, which form metal-peptide coordination complexes with various metal ions, can be used as biofunctional ingredients notably to enhance human health and prevent diseases. This review aims to discuss recent insights into food-derived metal-chelating peptides, the strategies set up for their discovery, their study, and identification. After understanding the overall properties of metal-chelating peptides, their production from food-derived protein sources and their potential applications will be discussed, particularly in nutritional, cosmetics and pharmaceutical fields. In addition, the review provides an overview of the last decades of progress in discovering food-derived metal-chelating peptides, addressing several screening, separation and identification methodologies. Furthermore, it emphasizes the methods used to assess peptide-metal interaction, allowing for better understanding of chemical and thermodynamic parameters associated with the formation of peptide-metal coordination complexes, as well as the specific amino acid residues that play important roles in the metal ion coordination.

Zinc deficiency and taste perception in the elderly.

Taste, one of the major senses in humans, is the ability to detect the flavor of substances such as food, certain minerals, and poisons. Taste distortions in human beings have been attributed to various physiological and environmental factors including aging and disease conditions. Given the fact that taste is one of the most important factors in food preference, selection, and consumption, the decreased appetite in the elderly, probably due to disease conditions, may lead to dietary restrictions that could negatively impact nutritional and health status. The role of zinc on taste distortion in the elderly population and taste impairment are described. Although several studies demonstrate the associative nature of taste degeneration with age, additional investigations are required to clarify the mechanisms by which taste perception is altered with age.

Aroma and taste perceptions with Alzheimer disease and stroke.

Chemosensory disorders of smell or taste in humans have been attributed to various physiological and environmental factors including aging and disease conditions. Aroma and taste greatly condition our food preference, selection and, consumption; the decreased appetite in patients with known neurodegenerative diseases may lead to dietary restrictions that could negatively impact nutritional and health status. The decline in olfactory and gustatory systems in patients with Alzheimer disease and various types of stroke are described.