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.

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.

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 poptides of differ-ent molecular weight were obtained and then their scavenging capacity of free radicals was measured. The molecular weight composition was stud-ied 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 fla-vourzyme respectively. All hydrolyzate with different molecular grades showed free radical scavenging capacity, which was increased with the reduc- tion 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.

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.

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.

Potential antioxidant bioactive peptides from camel milk proteins

Camel milk is traditionally considered to have medicinal characteristics that it has potential health benefits and could help to treat several illnesses. Particularly, it is closest to human breast milk and has high levels of nutrients and bioactive components. The aim of this study was to explore the antioxidant peptides derived from protein fractions of camel milk. Camel milk proteins(CMP) were fractionated into camel casein protein(CCP) and camel whey protein(CWP), which were hydrolyzed with pepsin to produce peptic digests P-CCP and P-CWP, respectively. RP-HPLC was used for fractionation of the peptides from the P-CCP and P-CWP. The antioxidant activities were evaluated using superoxide anion generating system of xanthine oxidase(XOD)and 2,2-diphenyl-1-picrylhydrazyl(DPPH) scavenging assay. Active peptides were analyzed using matrixassisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF-MS) whereas a number of antioxidant peptides, with masses ranging from 913 to 2,951 Da, derived mainly from alpha-casein, lactophorin and lactoferrin, were identified. When yeast cells are used as a system for modeling mitochondrial disease, the peptides in caseins and whey fractions significantly enhanced the tolerance of yeast cells against peroxide-induced oxidative stress. The results show that both caseins and whey proteins of camel milk possess bioactive peptides with significant radical-scavenging activities and thus herald a fascinating opportunity for their potential as nutraceuticals or therapeutic peptides for prevention and treatment of oxidative stress-associated diseases.

A comprehensive review on bioactive peptides derived from milk and milkproducts of minor dairy species

Milk from different species has been exploited for the isolation of various functional ingredients for decades.Irrespective of the source,milk is considered as a complete food,as it provides essential nutrients required by the human body.Proteins and their fractions are valuable sources of bioactive peptides that might exert a health beneficial role in the human body such as immune-modulation,antioxidant activity,ACE-inhibitory activity,anti-neoplastic,anti-microbial,etc.In milk,bioactive peptides may either be present in their natural form or released from their parental proteins due to enzymatic action.The increasing interest in bioactive peptides among researchers has lately augmented the exploration of minor dairy species such as sheep,goat,camel,mithun,mare,and donkey.Alternative to cow,milk from minor dairy species have also been proven to be healthier from infancy to older age owing to their higher digestibility and other nutritive components.Therefore,realizing the significance of milk from such species and incentivized interest towards the derivatization of bioactive peptides,the present review highlights the significant research achievements on bioactive peptides from milk and milk products of minor dairy species.

Effects of dairy bioactive peptides and lotus seeds/lily bulb powder on flavor and quality characteristics of goat milk yogurt

The objective of this study was to evaluate the changes on flavor and quality characteristics of goat yogurt during storage with the addition of dairy bioactive peptides and a mixture of lotus seed and lily bulb powder.Both the addition of dairy bioactive peptides and lotus seeds/lily bulb powder resulted in a fermentation time reduction,water holding capacity(WHC)improvement,and inhibition of post-acidification of goat yogurt during storage.A total of 50 volatile flavor components were detected in the goat milk yogurt samples,and the addition of the above two supplements were shown to be effective in improving the flavor and the textural properties of the goat milk yogurt during storage.The group added with lotus seeds/lily bulb powder showed the best WHC and textural properties,followed by the group added with dairy bioactive peptides alone and the group with both added.The addition of both supplements was found to be useful in making up for the two defects of goat yogurt,prolonged fermentation and soft curds.Therefore,dairy bioactive peptides and lotus seeds/lily bulb powder are recommended to be added to goat yogurt as nutritional supplements.

Bioactive peptides in fermented foods and their application:a critical review

Bioactive peptides are released during the production of fermented dairy,vegetables,fruits,legumes,fish,and meat prod-ucts.The proteolytic specificity of lactic acid bacteria,Bacillus spp.,yeasts,and mold,apart from their ability to synthesize bioactive peptides,plays an important role in the generation of specific bioactive peptides in traditional fermented foods.Controlled fermentation using defined starter strains has been explored for the development of bioactive peptides enriched novel fermented foods with potential functionality.Bioactive peptides enriched foods exert diverse health benefits,such as antioxidant,antihypertensive,antidiabetic,and immunomodulatory effects.Bioactive peptides can be used as alternatives to synthetic compounds due to negligible side effects and high valuation in the nutraceutical and functional food market.However,challenges associated with the identification,quantification,organoleptic properties,and bioavailability of bioac-tive peptides need to be addressed before exploiting the potential of bioactive peptides in the functional food industry.In the present review,we have discussed the production of bioactive peptides in diverse fermented foods.Structural and sequence specificity of peptides and their effect on the expression of distinct health beneficial effects have been described.The potential of utilizing these bioactive peptides for the development of novel functional fermented foods is discussed.Recent advances in peptide identification,quantification,debittering of peptides,and increasing peptide bioavailability have been explained.

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.

The alteration of gut microbiota by bioactive peptides:a review

Evidences suggest that the homeostasis of gut microbiota is among the most important factors for maintaining the physical and mental health of the host.Among the multiple factors affecting the homeostasis of gut microbiota,diet is one of the decisive factors.Bioactive peptides derived from protein hydrolyzed by protease or fermented by microorganism have many physiological activities that their parent proteins do not have.Currently,bioactive peptides attract more and more attention due to their bidirectional interaction with gut microbes.It has been reported that some bioactive peptides could alter the composition of gut microbiota by influencing the intestinal microenvironment.Meanwhile,quite a few bioactive peptides that are released by gut microbes or intestinal cells could resist the pathogenic bacteria to sustain the homeostasis of gut microbiota.In this review,some exogenous bioactive peptides derived from food and some endogenous bioactive peptides released from intestinal cells or microbes were discussed to summary their effects on the modulation of gut microbiota.This review is expected to provide new ideas for related research,and as well to promote the application of bioactive peptides in the fields of food and medicine.

Effects of periodical application of bioactive peptides derived from cottonseed on performance,immunity,total antioxidant activity of serum and intestinal development of broilers

This experiment aimed to examine the effect of periodical application of bioactive peptides derived from cottonseed(BPC)in comparison with using sub-therapeutic doses of lincomycin and the excessive in-clusion of vitamin E on performance,immunity,total antioxidant capacity of serum and intestinal morphology of broiler chickens.A total of 240 one-d-old male broiler chicks with similar initial weight(Ross strain)were randomly assigned to 6 groups(8 chicks/pen):non-treated group(basal diet),basal diet supplemented with 2 mg/kg lincomycin,basal diet supplemented with 50 IU vitamin E,basal diet supplemented with 6 g BPC/kg in starter period,basal diet supplemented with 6 g BPC/kg in starter and grower periods and basal diet supplemented with 6 g BPC/kg throughout the whole experiment.The highest final body weight was obtained in the group supplemented with BPC in starter and grower periods.In the finisher phase,broilers fed the diet containing BPC in the starter period and in the whole trial had significantly(P<0.05)better feed conversion ratios(FCR).Jejunal villus height was significantly elevated in broilers supplemented with antibiotic(P<0.001),furthermore it tended to be greater in broilers fed BPC in the starter period.The jejunal villus height-to-crypt depth ratio was significantly(P<0.01)higher in broilers fed the diet containing antibiotic in comparison to other groups.Humoral immune response against Newcastle disease vaccine tended to be elevated in broilers fed the diet containing BPC in the whole trial(P>0.05).Broilers supplemented with BPC in starter and grower,and in the whole trial had significantly(P<0.05)higher antibody titers against sheep red blood cells(SRBC).The highest total antioxidant capacity was obtained in broilers supplemented with the excessive level of vitamin E,furthermore it tended to improve in broilers fed the diet containing BPC in the whole trial.In summary,the results of the study indicated that addition of BPC in broiler diets in the whole trial could improve FCR,immune responses and total antioxidant activity of serum,and BPC could be used in broiler diets as an alternative to in-feed antibiotics.

Virtual screening and directional preparation of xanthine oxidase inhibitory peptides derived from hemp seed protein

The traditional nutritional and medical hemp(Cannabis sativa L.)seed protein were explored for the discovery and directional preparation of new xanthine oxidase inhibitory(XOI)peptides by structure-based virtual screening,compound synthesis,in vitro bioassay and proteolysis.Six subtypes of hemp seed edestin and albumin were in silico hydrolyzed by 29 proteases,and 192 encrypted bioactive peptides were screened out.Six peptides showed to be XOI peptides,of which four(about 67%)were released by elastase hydrolysis.The peptide DDNPRRFY displayed the highest XOI activity(IC50=(2.10±0.06)mg/mL),acting as a mixed inhibitor.The pancreatic elastase directionally prepared XOI hemp seed protein hydrolysates,from which 6 high-abundance XOI peptides encrypted 3 virtually-screened ones including the DDNPRRFY.The novel outstanding hemp seed protein-derived XOI peptides and their virtual screening and directed preparation methods provide a promising and applicable approach to conveniently and efficiently explore food-derived bioactive peptides.

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.

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.

Alginate-Casein Microspheres as Bioactive Vehicles for Nutrients

The aim of this work was to develop an alginate-casein composite microsphere as a bioaetive vehicle for oral administration of nutrients by a simple extrusion dripping method. Riboflavin was selected as a model drug, and the microencapsulation efficiency was raised to 97.94% after optimizing the preparation conditions by response surface methodology. In vitro release studies showed that riboflavin was released completely from alginate-casein microspheres in simulated intestinal fluids. Meanwhile, the morphology, structure and interaction between alginate and casein were characterized by scanning electron microscopy （SEM） and Fourier transform infrared （FTIR） spectra.

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.

Biopeptides of Pyropia yezoensis and their potential health benefits: A review

Pyropia yezoensis(P.yezoensis)is a popular species of red algae that are commercially cultivated and consumed in East Asia,China,Japan,and Korea.The high protein content of P.yezoensis provides a source of multiple bioactive peptides exhibiting antioxidant,anti-inflammatory,antihypertensive,anticancer,tissue healing,immunomodulatory,and anticoagulant properties.Furthermore,many other biologically active substances in P.yezoensis,including carbohydrates,lipids,dietary fibers,and polyphenols,have shown potential health benefits and are important in both the food and agriculture industries.This review provides a detailed summary of researches over the last decade on the biological and medicinal properties of bioactive peptides.The information was extracted from various electronic resources,including Google Scholar,PubMed,MEDLINE,and Google Patents.