Bioactive Peptide Discovery from Edible Insects for Potential Applications in Human Health and Agriculture.

In the past decade, there has been fast-growing interest among researchers to discover bioactive peptides from edible insects and to evaluate their potential applications in the management of human, livestock, and plant health. This review summarizes current knowledge of insect-derived peptides and their potential role in tackling human health issues and solving agriculture problems by protecting crops and livestock against their pathogens. Numerous bioactive peptides have been identified from edible insect species, including peptides that were enzymatically liberated from insect proteins and endogenous peptides that occur naturally in insects. The peptides exhibited diverse bioactivities, encompassing antioxidant, anti-angiotensin-converting enzyme, anti-dipeptidyl peptidase-IV, anti-glucosidase, anti-lipase, anti-lipoxygenase, anti-cyclooxygenase, anti-obesity, and hepatoprotective activities. Such findings point to their potential contribution to solving human health problems related to inflammation, free radical damage, diabetes, hypertension, and liver damage, among others. Although most of the experiments were performed in vitro, evidence for the in vivo efficacy of some peptides is emerging. Evidence of the protective effects of insect-derived endogenous antimicrobial peptides in combating farm animal and plant pathogens is available. The ability of insect-derived endogenous neuropeptides to protect plants against herbivorous insects has been demonstrated as well. Nevertheless, the potency of peptides identified from insect protein hydrolysates in modulating livestock and plant health remains a knowledge gap to be filled.

Evaluation of electro-assisted phytoremediation (EAPR) system for heavy metal removal from synthetic leachate using Pistia stratiotes.

The highest waste generated in Malaysia is composed of municipal solid waste, which is mainly managed by landfilling. Heavy metals in leachate generated from landfill could have caused hazardous effects to human and environment. EAPR has been increasingly applied to treat soil and wastewater. This technique serves as a potential tool for remediation of real leachate. Metals (Mn, Cd, Fe, Ni, Pb, Zn) uptake by Pistia stratiotes were evaluated via flame atomic adsorption spectrophotometer. Pb and Fe could be the elements that were more efficiently removed by P. stratiotes in the EAPR system. The removal efficiency was 59.86 ± 9.98 and 56.56 ± 18.08% for Pb and Fe, respectively. EAPR significantly reduced the BOD (9.37 ± 2.36 mg/L), color (120.00 ± 5.77 PtCo), and turbidity (25.50 ± 11.96 NTU) of synthetic leachate. An obvious accumulation of heavy metals was observed at roots based on BCF and TF values. BCF values of Pb (18,999.06 ± 8,321.76) and Fe (16,090.81 ± 5,844.36) in the EAPR system were more than 103, which indicates that P. stratiotes is a hyperaccumulator. Further study on the upregulated genes is needed to comprehend the molecular basis of heavy metal stress tolerance.

EAPR greatly reduced heavy metals, BOD, color, and turbidity of synthetic leachate. The use of water lettuce in EAPR could be another plant alternative for potential remediation of real leachate which is extremely difficult to be treated.

Seafood Paramyosins as Sources of Anti-Angiotensin-Converting-Enzyme and Anti-Dipeptidyl-Peptidase Peptides after Gastrointestinal Digestion: A Cheminformatic Investigation.

Paramyosins, muscle proteins occurring exclusively in invertebrates, are abundant in seafoods. The potential of seafood paramyosins (SP) as sources of anti-angiotensin-converting-enzyme (ACE) and anti-dipeptidyl-peptidase (DPP-IV) peptides is underexplored. This in silico study investigated the release of anti-ACE and anti-DPP-IV peptides from SP after gastrointestinal (GI) digestion. We focused on SP of the common octopus, Humboldt squid, Japanese abalone, Japanese scallop, Mediterranean mussel, Pacific oyster, sea cucumber, and Whiteleg shrimp. SP protein sequences were digested on BIOPEP-UWM, followed by identification of known anti-ACE and anti-DPP-IV peptides liberated. Upon screening for high-GI-absorption, non-allergenicity, and non-toxicity, shortlisted peptides were analyzed via molecular docking and dynamic to elucidate mechanisms of interactions with ACE and DPP-IV. Potential novel anti-ACE and anti-DPP-IV peptides were predicted by SwissTargetPrediction. Physicochemical and pharmacokinetics of peptides were predicted with SwissADME. GI digestion liberated 2853 fragments from SP. This comprised 26 known anti-ACE and 53 anti-DPP-IV peptides exhibiting high-GI-absorption, non-allergenicity, and non-toxicity. SwissTargetPrediction predicted three putative anti-ACE (GIL, DL, AK) and one putative anti-DPP-IV (IAL) peptides. Molecular docking found most of the anti-ACE peptides may be non-competitive inhibitors, whereas all anti-DPP-IV peptides likely competitive inhibitors. Twenty-five nanoseconds molecular dynamics simulation suggests the stability of these screened peptides, including the three predicted anti-ACE and one predicted anti-DPP-IV peptides. Seven dipeptides resembling approved oral-bioavailable peptide drugs in physicochemical and pharmacokinetic properties were revealed: AY, CF, EF, TF, TY, VF, and VY. In conclusion, our study presented in silico evidence for SP being a promising source of bioavailable and safe anti-ACE and anti-DPP-IV peptides following GI digestions.

New Advances in Short Peptides: Looking Forward.

It is beyond doubt that short peptides hold significant promise in bio-medicine, as the most versatile molecules, both structurally and functionally [...].

Computational Screening for the Anticancer Potential of Seed-Derived Antioxidant Peptides: A Cheminformatic Approach.

Some seed-derived antioxidant peptides are known to regulate cellular modulators of ROS production, including those proposed to be promising targets of anticancer therapy. Nevertheless, research in this direction is relatively slow owing to the inevitable time-consuming nature of wet-lab experimentations. To help expedite such explorations, we performed structure-based virtual screening on seed-derived antioxidant peptides in the literature for anticancer potential. The ability of the peptides to interact with myeloperoxidase, xanthine oxidase, Keap1, and p47phox was examined. We generated a virtual library of 677 peptides based on a database and literature search. Screening for anticancer potential, non-toxicity, non-allergenicity, non-hemolyticity narrowed down the collection to five candidates. Molecular docking found LYSPH as the most promising in targeting myeloperoxidase, xanthine oxidase, and Keap1, whereas PSYLNTPLL was the best candidate to bind stably to key residues in p47phox. Stability of the four peptide-target complexes was supported by molecular dynamics simulation. LYSPH and PSYLNTPLL were predicted to have cell- and blood-brain barrier penetrating potential, although intolerant to gastrointestinal digestion. Computational alanine scanning found tyrosine residues in both peptides as crucial to stable binding to the targets. Overall, LYSPH and PSYLNTPLL are two potential anticancer peptides that deserve deeper exploration in future.

A Global Review on Short Peptides: Frontiers and Perspectives.

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

The influences of thermal processing on phytochemicals and possible routes to the discovery of new phytochemical conjugates.

In our diets, many of the consumed foods are subjected to various forms of heating and thermal processing. Besides enhancing the taste, texture, and aroma of the foods, heating helps to sterilize and facilitate food storage. On the other hand, heating and thermal processing are frequently reported during the preparation of various traditional herbal medicines. In this review, we intend to highlight works by various research groups which reported on changes in phytochemicals and bioactivities, following thermal processing of selected plant-derived foods and herbal medicines. Relevant cases from plant-derived foods (garlic, coffee, cocoa, barley) and traditional herbal medicines (Panax ginseng, Polygonum multiforum, Aconitum carmichaelii Debeaux, Angelica sinensis Radix) will be presented in this review. Additionally, related works using pure phytochemical compounds will also be highlighted. In some of these cases, the amazing formation of new compounds were being reported. Maillard reaction could be concluded as the predominant pathway leading to the formation of new conjugates, along with other possibilities being suggested (degradation, transglycosylation, deglycosylation and dehydration). With collective efforts from all researchers, it is hoped that more details will be revealed and lead to the possible discovery of new, heat-mediated phytochemical conjugates.

Seeds, fermented foods, and agricultural by-products as sources of plant-derived antibacterial peptides.

The emergence of bacterial resistance against conventional antibiotics and the growing interest in developing alternative, natural antibacterial agents have prompted the search for plant-derived antibacterial peptides in recent decades. Different classes of endogenous antibacterial peptides have been identified from various plant species. Moreover, protein hydrolysates and hydrolysate-derived peptides with potent antibacterial effects have also been identified from numerous plant sources. Antibacterial peptides are often cationic and amphipathic, consisting of fewer than 100 amino acids. They are able to disrupt bacterial membrane integrity via pore formation and/or compromise bacterial metabolic processes. In this review, we summarize current knowledge on the characteristics and modes of action of antibacterial peptides, as well as salient points concerning the production of antibacterial protein hydrolysates from plant proteins. Examples of plant-derived antibacterial hydrolysates and peptides will be highlighted, with particular attention to less explored seeds, fermented plant foods and agricultural by-products. Promising future research directions with regards to the application of plant-derived antibacterial hydrolysates and peptides in food preservation, farm animal disease management, and nutraceutical/functional food development will be proposed.

Phytochemicals from fern species: potential for medicine applications.

Ferns are an important phytogenetic bridge between lower and higher plants. Historically they have been used in many ways by humans, including as ornamental plants, domestic utensils, foods, and in handicrafts. In addition, they have found uses as medicinal herbs. Ferns produce a wide array of secondary metabolites endowed with different bioactivities that could potentially be useful in the treatment of many diseases. However, there is currently relatively little information in the literature on the phytochemicals present in ferns and their pharmacological applications, and the most recent review of the literature on the occurrence, chemotaxonomy and physiological activity of fern secondary metabolites was published over 20 years ago, by Soeder (Bot Rev 51:442-536, 1985). Here, we provide an updated review of this field, covering recent findings concerning the bioactive phytochemicals and pharmacology of fern species.

Enzyme-Assisted Discovery of Antioxidant Peptides from Edible Marine Invertebrates: A Review.

Marine invertebrates, such as oysters, mussels, clams, scallop, jellyfishes, squids, prawns, sea cucumbers and sea squirts, are consumed as foods. These edible marine invertebrates are sources of potent bioactive peptides. The last two decades have seen a surge of interest in the discovery of antioxidant peptides from edible marine invertebrates. Enzymatic hydrolysis is an efficient strategy commonly used for releasing antioxidant peptides from food proteins. A growing number of antioxidant peptide sequences have been identified from the enzymatic hydrolysates of edible marine invertebrates. Antioxidant peptides have potential applications in food, pharmaceuticals and cosmetics. In this review, we first give a brief overview of the current state of progress of antioxidant peptide research, with special attention to marine antioxidant peptides. We then focus on 22 investigations which identified 32 antioxidant peptides from enzymatic hydrolysates of edible marine invertebrates. Strategies adopted by various research groups in the purification and identification of the antioxidant peptides will be summarized. Structural characteristic of the peptide sequences in relation to their antioxidant activities will be reviewed. Potential applications of the peptide sequences and future research prospects will also be discussed.

Phytochemical-mediated Protein Expression Profiling and the Potential Applications in Therapeutic Drug Target Identifications.

Many phytochemicals derived from edible medicinal plants have been investigated intensively for their various bioactivities. However, the detailed mechanism and their corresponding molecular targets frequently remain elusive. In this review, we present a summary of the research works done on phytochemical-mediated molecular targets, identified via proteomic approach. Concurrently, we also highlighted some pharmaceutical drugs which could be traced back to their origins in phytochemicals. For ease of presentation, these identified protein targets were categorized into two important healthcare-related fields, namely anti-bacterial and anti-cancer research. Through this review, we hope to highlight the usefulness of comparative proteomic as a powerful tool in phytochemical-mediated protein target identifications. Likewise, we wish to inspire further investigations on some of these protein targets identified over the last few years. With contributions from all researchers, the accumulative efforts could eventually lead to the discovery of some target-specific, low-toxicity therapeutic agents.

Cytotoxic, Antitumor and Immunomodulatory Effects of the Water-Soluble Polysaccharides from Lotus (Nelumbo nucifera Gaertn.) Seeds.

Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water-soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg) treatment (50.79%). The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01), while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent.

HPLC PROFILING OF PHENOLIC ACIDS AND FLAVONOIDS AND EVALUATION OF ANTI-LIPOXYGENASE AND ANTIOXIDANT ACTIVITIES OF AQUATIC VEGETABLE LIMNOCHARIS FLAVA.

Limnocharis flava is an edible wetland plant, whose phenolic acid and flavonoid compositions as well as bioactivities were underexplored. This study analyzed the profiles of selected hydroxybenzoic acids, hydroxycinnamic acids and flavonoids in the aqueous extracts of L. flava leaf, rhizome and root by high performance liquid chromatography (HPLC). Anti-lipoxygenase and antioxidant (iron chelating, 2,2-diphenyl-l-picrylhydrazyl (DPPH) radical scavenging, and nitric oxide (NO) scavenging) activities of the extracts were also evaluated. Leaf extract had the highest phenolic contents, being most abundant in p-hydroxybenzoic acid (3861.2 nmol/g dry matter), ferulic acid (648.8 nmol/g dry matter), and rutin (4110.7 nmol/g dry matter). Leaf extract exhibited the strongest anti-lipoxygenase (EC50 6.47 mg/mL), iron chelating (EC50 6.65 mg/mL), DPPH scavenging (EC50 15.82 mg/mL) and NO scavenging (EC50 3.80 mg/mL) activities. Leaf extract also had the highest ferric reducing ability. This is the most extensive HPLC profiling of phenolic acids and flavonoids in L.flava to date. In conclusion, L. flava leaf is a source of health-promoting phenolics, anti-lipoxygenase agents and antioxidants.

Extraction and characterization of cellulose nanoparticles from palm kernel meal for potential application in active food packaging.

The research aimed to explore the potential of palm kernel meal (PKM) as a sustainable source of cellulose nanoparticles (CNPs) for active food packaging. The CNPs were isolated using a combination of chemical techniques, such as alkaline treatment, bleaching, and acid hydrolysis. The characterization of the CNPs was analysed using various techniques, including scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and UV-visible spectroscopy. The findings revealed that chemical processing effectively removed lignin and hemicellulose from PKM. The SEM morphology confirmed the separation of the CNPs, resulting in the production of 40-100 nm spherical cellulose nanoparticles, while XRD and FTIR analyses confirmed their purity and composition. Moreover, the UV-visible spectroscopy exhibited high transmittance rates, indicating the potential of CNPs as reinforcing agents for polymer matrices. The significance of utilising PKM as a valuable fibre source for extracting CNPs can be recommended for developing active food packaging.

Bioactive Peptides and Protein Hydrolysates as Lipoxygenase Inhibitors.

Lipoxygenases are non-heme iron-containing enzymes that catalyze the oxidation of polyunsaturated fatty acids, resulting in the production of lipid hydroperoxides, which are precursors of inflammatory lipid mediators. These enzymes are widely distributed in humans, other eukaryotes, and cyanobacteria. Lipoxygenases hold promise as therapeutic targets for several human diseases, including cancer and inflammation-related disorders. Inhibitors of lipoxygenase have potential applications in pharmaceuticals, cosmetics, and food. Bioactive peptides are short amino acid sequences embedded within parent proteins, which can be released by enzymatic hydrolysis, microbial fermentation, and gastrointestinal digestion. A wide variety of bioactivities have been documented for protein hydrolysates and peptides derived from different biological sources. Recent findings indicate that protein hydrolysates and peptides derived from both edible and non-edible bioresources can act as lipoxygenase inhibitors. This review aims to provide an overview of the current knowledge regarding the production of anti-lipoxygenase protein hydrolysates and peptides from millet grains, chia seeds, insects, milk proteins, fish feed, velvet antler blood, fish scales, and feather keratins. The anti-lipoxygenase activities and modes of action of these protein hydrolysates and peptides are discussed. The strengths and shortcomings of previous research in this area are emphasized. Additionally, potential research directions and areas for improvement are suggested to accelerate the discovery of anti-lipoxygenase peptides in the near future.

A GmAOX2b antisense gene compromises vegetative growth and seed production in soybean.

The alternative oxidase mediates the cyanide-resistant respiratory pathway in plant mitochondria. In non-thermogenic plants, the role of alternative oxidase in plant growth and development is not well understood. Soybean (Glycine max) lines carrying a GmAOX2b antisense gene had compromised vegetative growth and reproductive performance under typical glasshouse growth conditions. The reduction in vegetative growth was demonstrated by reduction in shoot height, the number of leaves per plant and the green leaf area. Antisense plants also had decreased pod formation and seed to pod ratios, which together led to a reduction in the number and total mass of seed produced. The negative effects of the antisense gene on pod set, seed set, ovule availability and total seed mass were primarily confined to the branches, rather than the main stem. The preferential effect of alternative oxidase suppression in the branches is discussed in relation to the reproductive potential of soybean under stress. Taken together, these results demonstrate that alternative oxidase provides the benefit of sustaining plant vegetative growth and reproductive capacity in soybean.

Effects of Monascus application on in vitro digestion and fermentation characteristics of fish protein.

The aim of this study was to investigate the digestion and fermentation properties of fish protein fermented by Monascus. Semi-dried fish was fermented by applying Monascus purpureus Went M 3.439. Our results show that the Monascus fermentation of the fish protein enriched the free amino acids and achieved a relatively higher glutamate content than the control group. The Monascus treatment promoted the decomposition of the fish protein during in vitro digestion, reduced the ammonia and indole content and tended to increase the propionic acid content during in vitro fermentation. The Monascus treatment considerably changed the gut microbiota composition, and particularly increased the relative abundance of Parabacteroides in the in vitro fermentation model of human distal colon. Consumption of Monascus fermented fish protein could result in positive changes in fermentation metabolites and gut microbiota, which brings potential health benefits.

Photosynthetic performance and fertility are repressed in GmAOX2b antisense soybean.

The alternative oxidase (AOX) is a cyanide-resistant oxidase that provides an alternative outlet for electrons from the respiratory electron transport chain embedded in the inner membrane of plant mitochondria. Examination of soybean (Glycine max) plants carrying a GmAOX2b antisense gene showed AOX to have a central role in reproductive development and fecundity. In three independently transformed antisense lines, seed set was reduced by 16% to 43%, whereas ovule abortion increased by 1.2- to 1.7-fold when compared with nontransgenic transformation control plants. Reduced fecundity was associated with reductions in whole leaf cyanide-resistant, salicylhydroxamic acid-sensitive respiration and net photosynthesis, but there was no change in total respiration in the dark. The frequency of potential fertilization events was reduced by at least one-third in the antisense plants as a likely consequence of prefertilization defects. Pistils of the antisense plants contained a higher proportion of immature-sized, nonfertile embryo sacs compared with nontransgenic control plants. Increased rates of pollen abortion in vivo and reduced rates of pollen germination in vitro suggested that the antisense gene compromised pollen development and function. Reciprocal crosses between antisense and nontransgenic plants revealed that pollen produced by antisense plants was less active in fertilization. Taken together, the results presented here indicate that AOX expression has an important role in determining normal gametophyte development and function.

SARS-CoV-2 spike protein-, main protease- and papain-like-protease-targeting peptides from seed proteins following gastrointestinal digestion: An in silico study.

Background: The anti-COVID-19 potential of phytochemicals was investigated in numerous studies, but efficacy of peptides released by seed proteins upon gastrointestinal (GI) digestion is underexplored. Purpose: This study investigated whether multi-target anti-COVID-19 peptides could be released from edible seeds following GI digestion, by using in silico and molecular docking approaches. Methods: Nineteen seed storage proteins from Chenopodium quinoa (quinoa), Sesamum indicum (sesame), Brassica napus (rape), Helianthus annuus (sunflower) and Cucurbita maxima (pumpkin) seeds were subjected to in silico GI digestion, in order to detect the released peptides with high GI absorption that concurrently target the spike protein, main protease and papain-like protease of SARS-CoV-2. Results: Molecular docking study revealed that 36 peptides with high GI absorption, out of the 1593 peptides released from seed proteins, could bind to the binding or catalytic sites of the spike protein, main protease and papain-like protease of SARS-CoV-2, after GI digestion. Among the five seeds, quinoa was predicted to release the largest number (27) of multi-target peptides. When compared with PIY (Pro-Ile-Tyr), a high-GI-absorption fragment released from a potential anti-COVID-19 peptide, pumpkin-derived peptide PW (Pro-Trp) could bind more strongly to SARS-CoV-2 spike protein. PW was superior to some previously reported anti-SARS-CoV-2 phytochemicals when binding affinities towards the three viral targets were compared. Conclusion: Edible seeds are a potential source of anti-COVID-19 peptides upon GI digestion, hence they should be considered as an alternative to assist in the treatment and management of COVID-19.

Plant Bioactive Peptides: Current Status and Prospects Towards Use on Human Health.

Large numbers of bioactive peptides with potential applications in protecting against human diseases have been identified from plant sources. In this review, we summarized recent progress in the research of plant-derived bioactive peptides, encompassing their production, biological effects, and mechanisms. This review focuses on antioxidant, antimicrobial, antidiabetic, and anticancer peptides, giving special attention to evidence derived from cellular and animal models. Studies investigating peptides with known sequences and well-characterized peptidic fractions or protein hydrolysates will be discussed. The use of molecular docking tools to elucidate inter-molecular interactions between bioactive peptides and target proteins is highlighted. In conclusion, the accumulating evidence from in silico, in vitro and in vivo studies to date supports the envisioned applications of plant peptides as natural antioxidants as well as health-promoting agents. Notwithstanding, much work is still required before the envisioned applications of plant peptides can be realized. To this end, future researches for addressing current gaps were proposed.