Review on plant-derived bioactive peptides:biological activities,mechanism of action and utilizations in food development

Plant proteins are good alternative to animal sources in bioactive peptide production due to their safety,low-cost,rich resources and easy for large scale production.The bioactivities of the peptides derived from plant proteins including antihypertensive,hypocholesterolemic,immunomodulatory,antioxidant,antimicrobial,anti-diabetic,opiate and hepatoprotective effect are being increasingly recognized with regards to health promoting and disease prevention.In addition to bioactivities,the plant-derived bioactive peptides possess various functional properties including emulsifying and foaming properties,and water and oil retention capacities owning to the hydrophilic/lipophilic property,conformational flexibility and chain length of peptides.Hence,the plant-derived bioactive peptides are promising ingredients for the development of health-care and functional products.This review provides the research progress on the biological activities and functional properties of plant derived peptides.The mechanism of action and structure-activity relationships of the bioactive peptide were also described,when known.Furthermore,recent developments,major challenges and prospect in the application of the plant-derive bioactive peptides in the development of functional products are discussed and summarized.The objective of this review is to improve the understanding of plant-derive bioactive peptides,and provide some constructive inspirations for further research and industrial application in the food and medicine industry.

Transcriptomic analysis of Andrias davidianus meat and experimental validation for exploring its bioactive components as functional foods

Andrias davidianus(Chinese giant salamander,CGS)is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China.However,the progress of functional peptides mining was slow due to lack of reference genome and protein sequence data.In this study,we illustrated full-length transcriptome sequencing to interpret the proteome of CGS meat and obtain 10703 coding DNA sequences.By functional annotation and amino acid composition analysis,we have discovered various genes related to signal transduction,and 16 genes related to longevity.We have also found vast variety of functional peptides through protein coding sequence(CDS)analysis by comparing the data obtained with the functional peptide database.Val-Pro-Ile predicted by the CDS analysis was released from the CGS meat through enzymatic hydrolysis,suggesting that our approach is reliable.This study suggested that transcriptomic analysis can be used as a reference to guide polypeptide mining in CGS meat,thereby providing a powerful mining strategy for the bioresources with unknown genomic and proteomic sequences.

Computational biology in topical bioactive peptide discovery for cosmeceutical application:a concise review

Regenerative medicine and anti-aging research have made great strides at the molecular and cellular levels in dermatology and the medical aesthetic field,targeting potential treatments with skin therapeutic and intervention pathways,which make it possible to develop effective skin regeneration and repair ingredients.With the rapid development of computational biology,bioinformatics as well as artificial intelligence(A.I.),the development of new ingredients for regenerative medicine has been greatly accelerated,and the success rate has been improved.Some application cases have appeared in topical skin regeneration and repair scenarios.This review will briefly introduce the application of bioactive peptides in skin repair and anti-aging as emerging ingredients in cosmeceutics and emphasize how A.I.based computational biology technology may accelerate the development of innovative peptide molecules and ultimately translate them into potential skin regenerative and anti-aging scenarios.Typically,two research routines have been summarized and current limitations as well as directions were discussed for border applications in future research.

Molecular characteristics and structure–activity relationships of food-derived bioactive peptides

Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive peptides contain a great deal of development potential.More specifically,food-derived bioactive peptides have the advantages of a wide variety of sources,unique structures,high efficiency and safety,so they have broad development prospects.This review provides an overview of the current advances regarding the preparation,functional characteristics,and structure–activity relationships of food-derived bioactive peptides.Moreover,the prospects for the future development and application of food-derived bioactive peptides are discussed.This review may provide a better understanding of foodderived bioactive peptides,and some constructive inspirations for further research and applications in the food industry.

Isolation and identification of novel casein-derived bioactive peptides and potential functions in fermented casein with Lactobacillus helveticus

The present study here establishes a complete and effective method for isolating,purifying and identifying extracellular and intracellular peptides,and also describes the characters and bioactivities of peptides from fermented casein with Lactobacillus helveticus.Intracellular peptides are much larger in quantity and more complex in composition than extracellular peptides,between which the correlation reveals proteolytic and metabolic mechanisms.In addition,totally 241 different peptide sequences were identified by Nano LC–MS/MS from casein(212)and Lactobacillus helveticus proteins(29).These casein-derived peptides mostly originated from-casein,followed byS1-casein,-casein,andS2-casein,and came from extracell(69)and intracell(143),in which common peptides have a total of 27.Forty-four of the identified peptides were previously described as bioactive,including angiotensinconverting enzyme(ACE)-inhibitory,antioxidant,immunomodulating,antimicrobial,DPP-IV inhibitory,antiamnesic and anticancer effects and so on.Thirteen peptides with the potential of some biological activities are obtained,which were described in previous studies.A total of 47 novel peptides of 5 to 26 amino acids that were not disclosed were obtained.The new sources of natural bioactive peptides may have the very high application value as potential new peptide drugs for treatment human diseases.The product peptide DELQDKIHPF found in both extracell and intracell was quantitatively analyzed using the MRM mode of UPLC-U3Q,23.1 and 9.76 ng/mL,respectively.The quantitative analysis of the potential bioactive peptide may also advance the production of peptide products in the future.

Screening of protease-producing marine yeasts for production of the bioactive peptides

Over 400 yeast strains from seawater and sediments were obtained, but only five strains named HN2 -3, N13d, N13C, Mb5 and HN3 - 2 among them could form clear zones around their colonies on the double plates with 2.0% casein. Peptides in the hydrolysate produced by the proteases from strains HN2 -3 and N13d had higher angiotensin I-converting-enzyme （ACE）-inhibitory activity. The two marine yeast strains were identified to be Aureobasidium pullulans according to the results of routine yeast identification and molecular methods. After purification of the proteases from the two marine yeast strains, it was found that the optimal pH for them was both 9.0, both of them were serine alkaline protease. However, the optimal temperature for the protease from the strain HN2 -3 was 52℃ while that from strain N13d was 48℃. ACE-inhibitory activity of the peptides in the hydrolysate of shrimp protein produced by the purified protease from the strain HN2 -3 was the highest while antioxidant activity in the hydrolysate of spirulina protein produced by the purified protease from the strain N13d was the highest.

Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats

The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration.However,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose,which limits their clinical benefits.Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth fa ctors and can activate the equivalent receptors but have simplified sequences and structures.In this study,we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth fa ctor mimetic peptides(Chi/PDA-Ps).We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides.In this study,we evaluated the biocompatibility of the Chi/P DA-Ps conduits.Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth fa ctor mimetic peptide synergistically promoted prolife ration of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro.The Chi/P DA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury.We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy.The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and re myelination was further resto red.These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.

A review on mechanisms of action of bioactive peptides against glucose intolerance and insulin resistance

Insulin resistance leads to impaired glucose metabolism by disrupting both insulin secretion and sensitivity.Insulin resistance plays a key role in the pathophysiology of type 2 diabetes and metabolic syndrome.Reviews on the mechanisms of action of bioactive peptides on glucose homeostasis and insulin resistance are scarce.The recent discoveries of pathways and target cells in the management of glucose and energy metabolism have opened up new opportunities for identification of novel bioactive peptides on enhancing adipocyte differentiation and insulin signaling,glucose uptake,cholecystokinin receptor expression and activation,as well as insulin mimetics and incretin stimulants.Examples of food-derived bioactive peptides with glucoregulatory properties include Trp-Glu-Lys-Ala-Phe-Lys-Asp-Glu-Asp(WEKAFKDED),Gln-Ala-MetPro-Phe-Arg-Val-Thr-Glu-Gln-Glu(QAMPFRVTEQE),Glu-Arg-Tyr-Pro-Ile-Leu(ERKPIL),Val-Phe-LysGly-Leu(VFKGL),Phe-Leu-Val(FLV),Val-Pro-Pro(VPP),Ile-Arg-Trp(IRW),Ala-Lys-Ser-Pro-Leu-Phe(AKSPLF),Ala-Thr-Gln-Pro-Leu-Phe(ATNPLF),Phe-Glu-Glu-Leu-Gln(FEELN),Leu-Ser-Val-Ser-Val-Leu(LSVSVL),Val-Arg-Ileu-Arg-Leu-Leu-Gln-Arg-Phe-Asn-Lys-Arg-Ser(VRIRLLQRFNKRS),and Ala-GlyPhe-Ala-Gly-Asp-Asp-Ala-Pro-Arg(AGFAGDDAPR).However,as yet,clinical evidence on the effi cacy of such bioactive peptides is rare but is inevitable to establish their applications against glucose intolerance and insulin resistance.

Effect of Bioactive Peptides(BPs) on the Development of Pacific White Shrimp(Litopenaeus vannamei Boone, 1931)

The present study was conducted to evaluate the feasibility of replacing fish meal(FM) with bioactive peptides(BPs) in diet of white shrimp(Litopenaeus vannamei). The changes in growth performance, body composition, non-specific immunity, and water quality were examined after the shrimp were fed four diets, in which 0%(control), 33.3%, 66.7% and 100% of FM was replaced by BPs, respectively. The groups were designated as Con, 1/3BPs, 2/3BPs, and 3/3BPs. A total of 720 shrimp with an initial body weight of 1.46 ± 0.78 g were fed the experimental diets for 56 days. The results revealed that: 1) the weight gain rate(WGR) in 1/3BPs, 2/3BPs, and 3/3BPs was significantly higher than that in Con(P < 0.05), while no significant difference was found on survival rate and feed conversion ratio(FCR); 2) the whole-body crude protein(CP) and crude lipids(CL) were significantly different among groups, while there was no significant difference between crude ash and phosphorus contents; 3) the levels of acid phosphatase(ACP), lysozyme(LZM), superoxide dismutase(SOD), phenol oxidase(PO) and bactericidal activity increased significantly with the inclusion of BPs; 4) in terms of water quality, no significant difference was found in p H and dissolved oxygen among diets during the whole experimental period. Moreover, even though nitrite and ammonium levels tended to increase with time, there was no significant difference among groups. The results indicated that BPs is an applicable alternative of protein source, which can substitute FM in the diets of L. vannamei; it is able to effectively promote growth performance and improve immunity. Moreover, BPs in the diets had no negative impact on water quality.

Study on the Molecular Weight Composition and Antioxidant Activity of Peanut Bioactive Peptides

[Objective]To prepare peanut bioactive peptides and analyze their molecular weight composition and antioxidant activity.[Method]The dialysis bag of 8.0,3.5 and 1.0 kD were used to classify the hydrolyzate derived from alcalase and flavourzyme,peanut bioactive peptides of different molecular weight were obtained and then their scavenging capacity of free radicals was measured.The molecular weight composition was studied by Tricine-SDS-PAGE.[Result]The content of peptides <1.0 kD were 76.21% and 83.42% in the total hydrolyzate from alcalase and flavourzyme respectively.All hydrolyzate with different molecular grades showed free radical scavenging capacity,which was increased with the reduction of molecular mass.The peptides <1.0 kD exhibited higher radical scavenging capacity of(87.41±0.66)%(alcalase)and(67.88±0.48)%(flavourzyme),respectively.[Conclusion]Peanut bioactive peptides had strong effect of antioxidant capacity,especially that <1.0 kD,which had great prospect.

A Study of Bioactivity of Corn Peptides with Low Molecular Weight Ⅱ: Effect on Plasma Free Amino Acid Concentrations in Rats

The effects of the ingestion of corn peptides with a low molecular weight(LMCP) prepared from zein on some plasma free amino acid concentrations in rats that had taken ethanol were investigated. LMCP(1 0 g/kg body weight) in 15% ethanol(10 mL/kg body weight) was given to Wister rats by intragastrical administration. The amino acid analysis showed that the concentrations of alanine, leucine, and proline in the plasma reached their maximum levels at 30 min for the LMCP-intake group. They are 582.39, 99.60 and 272.51 μg/L , respectively. But in the control group, the plasma free amino acid levels were not changed obviously. Therefore, LMCP could cause an increase in concentration of some free amino acids such as alanine, leucine and proline etc . in plasma of the rats that have taken ethanol.

Osteogenesis of MC3T3 Preosteoblasts on 3D Bioactive Peptide Modified Nano-Macroporous Bioactive Glass Scaffolds

Biointerface design that targets osteogenesis is a growing area of research with significant implications in biomedicine. Materials known to either support or stimulate osteogenesis are composed of a biomimetic ceramic material, such as bioactive glass. Bioactive glass is osteoproductive, and the potential for osteoproductivity can be enhanced by the addition of proteins or other additives designed to alter functionality. In addition, soluble growth factors are often added to osteogenic culture on bioactive glasses, further intensifying the effects of the material. In this paper, synthetic peptide combinations, covalently bound to a three-dimensional bioactive glass network, are used to mimic the effects of the whole fibronectin and bone morphogenetic proteins (BMP) 2 and 9. Peptide-silanes possessing critical binding sequences from each of these proteins are synthesized and used to decorate the surface of three-dimensional (3D) nano-macroporous bioactive glass. MC3T3 preosteoblast cells are then assessed for differentiation on the materials in the absence of soluble differentiation cues. MC3T3 preosteoblasts undergo enhanced differentiation on the peptide-silane samples over the standard nano-macroporous bioactive glass, and the differentiation capacity of the cells exposes only to peptide-silane surfaces approaches that of cells grown in chemical differentiation induction media.

Re-Densification Effect of Pressure-Injected Peptide-Hyaluronic Acid Combination on Male Androgenic Alopecia

Introduction: Mechanism of male androgenic alopecia (MAGA) is complex and leads to an excessive hair shedding and decreased hair density. Oral, topical, and injectable autologous treatments demonstrate ability to stimulate hair re-growth, but the response is suboptimal or plateaus off. Synthetic combination of the peptide complex and hyaluronic acid (P-HA) demonstrated hair regrowth in alopecia patients. Electronically-operated pneumatic injections (EPI) generate micro-trauma in the dermis and under wound-healing conditions may enhance regeneration effect of P-HA. Methods: Subjects seeking improvement of their male pattern hair loss (Hamilton-Norwood type 2-4) received the P-HA treatments through EPI. The course included 4 treatments every two weeks over the 8-week period. In 6 months, the hair growth was assessed comparative to baseline by global clinical photography and digital phototrichograms. The treatment safety and tolerability were documented through the whole study period. Results: Twelve men (30-45 years old) completed the treatment course with high tolerability and without adverse events. Post-treatment assessment of the previously bald areas showed improved coverage on the clinical photographs. The phototrichograms demonstrated statistically significant increase in terminal hair density by 36%, cumulative hair thickness by 37%, and follicular units by 20%;all contributing to a 38% increase in cumulated hair density (all p Conclusion: Electronic pneumatic injections are well tolerated and can be safely used for the needle-free administration of the peptide-hyaluronic acid combination in MAGA therapy. We achieved significant hair re-densification in the balding scalp. The exact role of the EPI-induced impact in the hair re-growth mechanism remains to be ascertained. .

Effect of 30%Xiange Oceanic Bioactive Peptide Pesticide-Fertilizer on Sugarcane Pests,Sugarcane Yield and Sugar

[Objective]The paper was to study the effect of 30%Xiange oceanic bioactive peptide pesticide-fertilizer on sugarcane pests,sugarcane yield and sugar.[Method]With conventional compound fertilizer mixed with 3%carbofuran granulated insecticide as the control,the field effect of30%Xiange pesticide-fertilizer on sugarcane was compared.[Result]After the application of 30%Xiange pesticide-fertilizer for 90 d,the control effects on sugarcane borers in the two test points were 93.66%and 93.09%,respectively,which were significantly higher than those of conventional control(21.86%and 24.19%).Before harvest,the reduction effects of sugarcane internodes in the two test points treated by pesticide-fertilizer were6.21%and 5.10%,respectively,which were significantly lower than those of conventional control(36.25%and 34.55%).The control effects of Xiange pesticide-fertilizer on sugarcane chafer in the two test points were 91.34%and 100.00%respectively,which were significantly higher than those of conventional control(68.00%and 64.29%).The yields of sugarcane treated by Xiange pesticide-fertilizer in the two test points were107700 and 108000 kg/hm2,and the sugar contents were 15.62%and 15.55%,respectively.The yield and sugar content of sugarcane treated by Xiange pesticide-fertilizer were increased by 28.63%and 1.33%compared with those of conventional control.[Conclusion]30%Xiange oceanic bioactive peptide pesticide-fertilizer has good control effect on sugarcane pests,which could obviously increase yield and sugar of sugarcane.The product is worth being promoted and applied in sugarcane planting area.

The selection of alkaline protease-producing yeasts from marine environments and evaluation of their bioactive peptide production

A total of 400 yeast strains from seawater,sediments,saltern mud,marine fish guts,and marine algae were obtained.The protease activity of the yeast cultures was estimated,after which four strains (HN3.11,N11b,YF04C and HN4.9) capable of secreting extracellular alkaline protease were isolated.The isolated strains were identified as Aureobasidium pullulans,Yarrowia lipolytica,Issatchenkia orientalis and Cryptococcus cf.aureus.The optimal pH of the protease activity produced by strains HN3.11,YF04C,and HN4.9 was 9.0,while that of the protease produced by strain N11b was 10.0.The optimal temperature for protease activity was 45°C for strains HN3.11,N11b,and YF04C,and 50°C for strain HN4.9.After digestion of shrimp (Penaeus vannamei) protein and spirulina (Arthospira platensis) protein with the four crude alkaline proteases,the filtrate from spirulina (Arthrospira platensis) powder digested by the crude alkaline protease of strain HN3.11 was found to have the highest antioxidant activity (61.4%) and the highest angiotensin I converting enzyme (ACE)-inhibitory activities (68.4%).The other filtrates had much lower antioxidant activity and ACE-inhibitory activities.

A Study on Anti-oxidative Activity of Soybean Peptideswith Linoleic Acid Peroxidation Systems

Soybean bioactive peptides（SBPs） were prepared from the isolated soybean protein by proteolysis with an alkaline protease, alcalase, at 50℃ and pH = 8.0. The dependence of hydrolysis time on hydrolysis degree and molecular weight distribution were examined. The hydrolysate was fractionated on a Sephadex G-25 column and the anti-oxidative activities of the fractions were detected by the method of pyrogallol auto-oxidation. The average chain length of soybean peptides that have anti-oxidative activity was estimated to be about 7. The anti-oxidative properties of the soy- bean peptide were also studied by using linoleic acid peroxidation systems. The optimal condition of the peroxidation system was set up, Vc/Cu^2 ＋ as the inducer at pH = 7.4 and 25 ℃. In addition, soybean peptides show higher antioxidative activity compared with GSH.

Endophytes as Producers of Peptides:An Overview About the Recently Discovered Peptides from Endophytic Microbes

An endophyte is a fungus or bacterium that lives within a plant in a symbiotic relationship.Extensive colonization of the plant tissue by endophytes creates a barrier effect,where they outcompete and prevent pathogenic organisms from taking hold.This happens by producing secondary metabolites that inhibit the growth of the competitors or pathogens.In this way they play a very important role in the plant defence mechanisms.The metabolites produced by these endophytes fall within a wide range of classes of compounds that include peptides which are the focus of this review.Peptides are increasingly being selected for drug development because they are specific for their targets and have a higher degree of interactions.There have been quite a number of endophytic peptides reported in the recent past indicating that endophytes can be used for the production of peptide based drugs.Molecular screening for NRPS,which shows peptide producing capability,has also shown that endophytes are potential producers of peptides.The presence of NRPS also offers the possibility of genetic modifications which may generate peptides with high pharmacological activities.This review,therefore,aims to show the current status of peptides isolated from endophytic bacteria and fungi in the recent decade.Endophytes as potential sources of peptides according to NRPS studies will also be discussed.

Antioxidant peptides encrypted in flaxseed proteome:An in silico assessment

Flaxseed proteins and antioxidant peptides(AP)encrypted in their sequences were analysed in silico with a range of bioinformatics tools to study their physicochemical properties,allergenicity,and toxicity.Nine proteases(digestive,plant and microbial sources)were assessed for their ability to release known APs from 23 mature flaxseed storage proteins using the BIOPEP database.The families of proteins identified were predominantly globulins,oleosins,and small amount of conlinin.Overall,253 APs were identified from these proteins.More peptides were released by enzymatic hydrolysis from the globulins than those from oleosins and conlinin.Compared with other enzymes studied,the plant proteases(papain,ficin,and bromelain)were found to be superior to releasing APs from the flaxseed proteins.Analysis of toxicity by ToxinPred showed that none of the peptides released was toxic.Most of the APs showed structural features that are important for antioxidation,including relatively low molecular weight(dipeptides and tripeptides only);amphipathic properties(hydrophobicity range of-0.5 to+0.5);relatively low Boman index(≤2);broad range of pI(3.7-10.8),and an abundance of antioxidant amino acid residues(e.g.glutamic acid and histidine).This study demonstrate the suitability of flaxseed proteins as a source of APs.

Occurrence,properties and biological significance of pyroglutamyl peptides derived from different food sources

Pyroglutamyl(pGlu)peptides are formed from intramolecular cyclization of glutamine or glutamic acid residue at the N-terminal position of peptides.This process can occur endogenously or during processing of foods containing the peptides.Some factors such as heat,high pressure and enzymatic modifications contribute to pGlu formation.pGlu peptides are thought to have different characteristics,especially bitter and umani tastes,and thus can affect the sensory properties of foods that contain them.Moreover,some health-promoting properties have been reported for pGlu peptides,including hepatoprotective,antidepressant and anti-inflammatory activities.However,the role of pGlu residue in the peptide bioactivity is not completely established,although the hydrophobic-lactam ring is thought to enhance the peptide stability against degradation by gastrointestinal proteases.This review discusses the occurrence and formation of pGlu peptides in foods,their quantification,sensory and biological properties,and prospects in food applications.