Rich Source Of Bioactive Peptides Research Articles

Using Constellation Pharmacology to Characterize a Novel α-Conotoxin from Conus ateralbus.

The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function of the various nAChR subtypes. By studying how conotoxins interact with nAChRs, we can improve our understanding of these receptors, leading to new insights into neurological diseases associated with nAChRs. Here, we describe the discovery and characterization of a novel conotoxin from Conus ateralbus, αCtx-AtIA, which has an amino acid sequence homologous to the well-described αCtx-PeIA, but with a different selectivity profile towards nAChRs. We tested the synthetic αCtx-AtIA using the calcium imaging-based Constellation Pharmacology assay on mouse DRG neurons and found that αCtx-AtIA significantly inhibited ACh-induced calcium influx in the presence of an α7 positive allosteric modulator, PNU-120596 (PNU). However, αCtx-AtIA did not display any activity in the absence of PNU. These findings were further validated using two-electrode voltage clamp electrophysiology performed on oocytes overexpressing mouse α3β4, α6/α3β4 and α7 nAChRs subtypes. We observed that αCtx-AtIA displayed no or low potency in blocking α3β4 and α6/α3β4 receptors, respectively, but improved potency and selectivity to block α7 nAChRs when compared with αCtx-PeIA. Through the synthesis of two additional analogs of αCtx-AtIA and subsequent characterization using Constellation Pharmacology, we were able to identify residue Trp18 as a major contributor to the activity of the peptide.

Profiling the Linear Peptides of Venom from the Brazilian Scorpion Tityus serrulatus: Structural and Functional Characterization.

Scorpion venoms are a rich source of bioactive peptides, most of which are neurotoxic, with 30 to 70 amino acid residues in their sequences. There are a scarcity of reports in the literature concerning the short linear peptides found in scorpion venoms. This type of peptide toxin may be selectively extracted from the venom using 50% (v/v) acetonitrile. The use of LC-MS and MS/MS enabled the detection of 12 bioactive short linear peptides, of which six were identified as cryptides. These peptides were shown to be multifunctional, causing hemolysis, mast cell degranulation and lysis, edema, pain, and anxiety, increasing the complexity of the envenomation mechanism. Apparently, the natural functions of these peptide toxins are to induce inflammation and discomfort in the victims of scorpion stings.

Screening and mechanism of six angiotensin I-converting eneyme inhibitory peptides from protein hydrolysate of Coregonus peled visceral: A combined in computer and in vitro study

Coregonus peled visceral can be regarded as a rich source of bioactive peptides. The purpose of this study is to screen peptides with high angiotensin I-converting eneyme (ACE) inhibitory activity from protein hydrolysate of Coregonus peled visceral prepared by trypsin, and analyze the inhibitory mechanisms of prepared peptides. The results showed that the UF-4 (MW < 3 kDa) had the highest ACE inhibitory activity of 73.55% (2 mg/ml). UF-4 was separated by Sephadex G-25 column and collected three fractions (F1, F2 and F3), and 397 peptides were detected from F1 fraction, and 6 peptides were screened by silico methods as potential antihypertensive peptides. FPGAKP formed 9 hydrogen bond interactions with Ala354, Tyr523, Glu384 in S1 pocket; His353 in S2 pocket; 5 hydrogen bond interactions with Thr282, Ala356, Arg522, Arg522, and His387 near the active sites. FPGAKP has the highest ACE inhibitory activity (IC50 = 0.039 mg/ml) and exhibits competitive inhibition. The total content of β-sheet and α-helix in the secondary structure of FPGAKP was the highest (80.22%). Studies have shown that the ACE inhibitory activity of the peptide mainly depends on the number of hydrogen bonds formed with the key active site of ACE and the content of β-sheet and α-helix. The results indicated that FPGAKP has the value of further research as a substitute for antihypertensive drugs.

Potential of Human Hemoglobin as a Source of Bioactive Peptides: Comparative Study of Enzymatic Hydrolysis with Bovine Hemoglobin and the Production of Active Peptide α137-141.

Cruor, the main component responsible for the red color of mammalian blood, contains 90% haemoglobin, a protein considered to be a rich source of bioactive peptides. The aim of the present study is to assess the potential of human hemoglobin as a source of bioactive peptides, compared with bovine hemoglobin, which has been extensively studied in recent years. More specifically, the study focused on the α137-141 fragment of bovine haemoglobin (TSKYR), a small (653 Da) hydrophilic antimicrobial peptide. In this work, the potential of human hemoglobin to contain bioactive peptides was first investigated in silico in comparison with bovine hemoglobin-derived peptides using bioinformatics tools. The blast results showed a high identity, 88% and 85% respectively, indicating a high similarity between the α and β chains. Peptide Cutter software was used to predict cleavage sites during peptide hydrolysis, revealing major conservation in the number and location of cleavage sites between the two species, while highlighting some differences. Some peptides were conserved, notably our target peptide (TSKYR), while others were specific to each species. Secondly, the two types of hemoglobin were subjected to similar enzymatic hydrolysis conditions (23 °C, pH 3.5), which showed that the hydrolysis of human hemoglobin followed the same reaction mechanism as the hydrolysis of bovine hemoglobin, the 'zipper' mechanism. Concerning the peptide of interest, α137-141, the RP-UPLC analyses showed that its identification was not affected by the increase in the initial substrate concentration. Its production was rapid, with more than 60% of the total α137-141 peptide production achieved in just 30 min of hydrolysis, reaching peak production at 3 h. Furthermore, increasing the substrate concentration from 1% to 10% (w/v) resulted in a proportional increase in α137-141 production, with a maximum concentration reaching 687.98 ± 75.77 mg·L-1, approximately ten-fold higher than that obtained with a 1% (w/v) concentration. Finally, the results of the UPLC-MS/MS analysis revealed the identification of 217 unique peptides in bovine hemoglobin hydrolysate and 189 unique peptides in human hemoglobin hydrolysate. Of these, 57 peptides were strictly common to both species. This revealed the presence of several bioactive peptides in both cattle and humans. Although some had been known previously, new bioactive peptides were discovered in human hemoglobin, such as four antibacterial peptides (α37-46 PTTKTYFPHF, α36-45 FPTTKTYFPH, α137-141 TSKYR, and α133-141 STVLTSKYR), three opioid peptides (α137-141 TSKYR,β31-40 LVVYPWTQRF,β32-40, VVYPWTQRF), an ACE inhibitor (β129-135 KVVAGVA), an anticancer agent (β33-39 VVYPWTQ), and an antioxidant (α137-141 TSKYR). To the best of our knowledge, these peptides have never been found in human hemoglobin before.

Synthesis and Biological Activity of Novel α-Conotoxins Derived from Endemic Polynesian Cone Snails.

α-Conotoxins are well-known probes for the characterization of the various subtypes of nicotinic acetylcholine receptors (nAChRs). Identifying new α-conotoxins with different pharmacological profiles can provide further insights into the physiological or pathological roles of the numerous nAChR isoforms found at the neuromuscular junction, the central and peripheral nervous systems, and other cells such as immune cells. This study focuses on the synthesis and characterization of two novel α-conotoxins obtained from two species endemic to the Marquesas Islands, namely Conus gauguini and Conus adamsonii. Both species prey on fish, and their venom is considered a rich source of bioactive peptides that can target a wide range of pharmacological receptors in vertebrates. Here, we demonstrate the versatile use of a one-pot disulfide bond synthesis to achieve the α-conotoxin fold [Cys 1-3; 2-4] for GaIA and AdIA, using the 2-nitrobenzyl (NBzl) protecting group of cysteines for effective regioselective oxidation. The potency and selectivity of GaIA and AdIA against rat nicotinic acetylcholine receptors were investigated electrophysiologically and revealed potent inhibitory activities. GaIA was most active at the muscle nAChR (IC50 = 38 nM), whereas AdIA was most potent at the neuronal α6/3 β2β3 subtype (IC50 = 177 nM). Overall, this study contributes to a better understanding of the structure-activity relationships of α-conotoxins, which may help in the design of more selective tools.

Transepithelial transport and cytoprotection of novel antioxidant peptides isolated from simulated gastrointestinal digestion of Xuanwei ham.

As a traditional fermented meat product, dry-cured Xuanwei ham could be a rich source of bioactive peptides. This study intended to investigate the transepithelial transport and cytoprotection of antioxidant peptides isolated from simulated gastrointestinal digestion of Xuanwei ham. Through ultrafiltration and gel filtration chromatography after simulated digestion, five new antioxidative cell-penetrating peptides (CPPs) with 16-27 amino acid residues were identified, and protective effects of the pretreatment with GHYTEGAELVDSVLDVVRK (GK-19) and TDEFQLHTNVNDGTEFGGSIYQK (TK-23) on H2O2-induced damaged HepG2 cells were investigated. The results showed that the peptide TK-23 at 0.5 mg mL-1 showed a good antioxidant activity through upregulating the activity of antioxidant enzymes (CAT, SOD and GR) and decreasing the MDA level in H2O2-induced damaged HepG2 cells with a better protective effect compared to GSH. Our observations of novel antioxidant CPPs with 16-27 amino acid residues could enrich the antioxidative CPP database, and these findings could provide data support for further study of CPPs.

Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond.

Peptides are potential therapeutic alternatives against global diseases, such as antimicrobial-resistant infections and cancer. Venoms are a rich source of bioactive peptides that have evolved over time to act on specific targets of the prey. Peptides are one of the main components responsible for the biological activity and toxicity of venoms. South American organisms such as scorpions, snakes, and spiders are important producers of a myriad of peptides with different biological activities. In this review, we report the main venom-derived peptide families produced from South American organisms and their corresponding activities and biological targets.

Pearl millet protein hydrolysates exhibiting effective in‐vitro antioxidant, antidiabetic and anti‐lipidemic properties as potential functional food ingredient

SummaryMillets are well‐known for protein with high nutritional value and a range of health benefits. Millet‐derived proteins can thus be a rich source of bioactive peptides with multiple bioactive properties. In this study three proteolytic enzymes, i.e. alcalase, bromelain, and chymotrypsin were used to generate pearl millet protein hydrolysates (PMPHs) and explored for multifunctional bioactive properties. Degree of hydrolysis (DH) ranged between 28.69% and 59.21% with maximum DH observed for PMPs hydrolysed with bromelain for 9 h. The PMPs digested with alcalase exhibited enhanced in‐vitro anti‐diabetic potential with greater inhibition towards α‐amylase and dipeptidyl peptidase‐IV (DPP‐IV) with IC50 inhibitory concentration of 5.06 and 3.44 μg mL−1, respectively. Alcalase PMPHs demonstrated the strongest ABTS radical scavenging activity (976 mM TEAC) while chymotrypsin‐generated PMPHs showed significant scavenging of DPPH free radicals (222.3 mM TEAC). In addition, bromelain‐treated hydrolysates displayed the highest α‐glucosidase inhibitory activity (6.71 μg mL−1) and Ferric reducing anti‐oxidant power (585.7 mM TEAC). Moreover, PMPHs generated by alcalase showed potential anti‐lipidemic activity by inhibiting pancreatic lipase and cholesteryl esterase with maximum IC50 values of 3.46 and 3.61 μg mL−1, respectively. These findings suggest that PMPs could be used as a potential source for bioactive hydrolysates with improved anti‐diabetic, anti‐lipidemic, and anti‐oxidant activities.

Anti-Melanogenesis Activity of Crocodile (Crocodylus siamensis) White Blood Cell Extract on Ultraviolet B-Irradiated Melanocytes.

Ultraviolet (UV) radiation generates a range of biological effects in the skin, which includes premature skin aging, hyperpigmentation, and cancer. Therefore, the development of new effective agents for UV-related skin damage remains a challenge in the pharmaceutical industry. This study aims to test the inhibitory effect of crocodile white blood cell (cWBC) extract, a rich source of bioactive peptides, on ultraviolet B (UVB)-induced melanocyte pigmentation. The results showed that cWBC (6.25-400 μg/mL) could inhibit tyrosinase without adduct formation by 12.97 ± 4.20% on average. cWBC pretreatment (25-100 μg/mL) had no cytotoxicity and reduced intracellular melanin to 111.17 ± 5.20% compared with 124.87 ± 7.43 for UVB condition. The protective role of cWBC pretreatment against UVB was exhibited by the promotion of cell proliferation and the prevention of UVB-induced morphological change as observed from F actin staining. The decrease of microphthalmia-associated transcription factor expression levels after cWBC pretreatment might be a mechanism by which cWBC suppresses UVB-induced pigmentation. These results suggest that cWBC could be beneficial for the prevention of UVB-induced skin pigmentation.

In silico prediction of peptide variants from chia (S. hispanica L.) with antimicrobial, antibiofilm, and antioxidant potential

Plants are known as a rich source of bioactive peptides, and a variety of plant peptides have been studied as potential alternatives to conventional antimicrobial, antibiofilm, and antioxidant agents in food products to prolong their shelf-life, which could pose potential health risks for consumers. Regardless of their high functional potential, no plant peptides are currently used in the food industry for these purposes. In this study, it is performed the selection and optimization of peptides that are not currently reported in any database, derived from a chia peptide fraction. Computer-aided tools were used to identify multifunctional peptides with antimicrobial, antibiofilm, and antioxidant potential. Two peptide sequences (YACLKVK and KLKKNL) showing the highest probability scores for antimicrobial activity were identified from a total of 1067 de novo sequences in a chia peptide fraction (F<1 kDa). Subsequently, the peptides YACLKVK and KLKKNL were used to create scrambled libraries containing permutations of these sequences to explore the antibiofilm potential of different amino acid arrangements. The peptide variants with the highest probability scores for antibiofilm activity were subjected to optimization for the improvement of their activity. Finally, the optimized sequences were analyzed to determine the presence of antioxidant fragments. This computational approach could be a solution for the screening of a large number of peptides with more than one function, allowing the development of multifunctional peptides as alternatives to traditional food preservatives.

Exploring Marine as a Rich Source of Bioactive Peptides: Challenges and Opportunities from Marine Pharmacology.

This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to obtain or extract high-value MBPs from touched/untouched sources. For instance, marine microorganisms, including microalgae, bacteria, fungi, and marine polysaccharides, are considered prolific sources of amino acids at large, and peptides/polypeptides in particular, with fundamental structural sequence and functional entities of a carboxyl group, amine, hydrogen, and a variety of R groups. Thus, MBPs with tunable features, both structural and functional entities, along with bioactive traits of clinical and therapeutic value, are of ultimate interest to reinforce biomedical settings in the 21st century. On the other front, as the largest biome globally, the marine biome is the so-called “epitome of untouched or underexploited natural resources” and a considerable source with significant potentialities. Therefore, considering their biological and biomedical importance, researchers around the globe are redirecting and/or regaining their interests in valorizing the marine biome-based MBPs. This review focuses on the widespread bioactivities of MBPs, FDA-approved MBPs in the market, sustainable development goals (SDGs), and legislation to valorize marine biome to underlying the impact role of bioactive elements with the related pathways. Finally, a detailed overview of current challenges, conclusions, and future perspectives is also given to satisfy the stimulating demands of the pharmaceutical sector of the modern world.

The effects of whey proteins, their peptides and amino acids on vascular function.

Cardiovascular diseases (CVD) are a significant and growing burden on global health services, and it is now accepted that impairment of vascular function represents a major preliminary step in the development of CVD. There is considerable interest in identifying both causal factors of impaired vascular function, as well as related nutritional factors that may lower the risk of developing CVD, and food-derived bioactive peptides and amino acids have emerged as one such area. Dairy foods contain two groups of proteins, whey proteins and caseins, which represent a rich source of bioactive peptides that are released during food processing and/or digestion. These peptides have a number of physiological activities including the potential to reduce blood pressure. Research, including acute and longer-term randomised controlled trials, animal models and in vitro models has demonstrated the potential impact of dairy proteins on vascular function. The purpose of this paper is to narratively review the evidence, primarily from randomised controlled trials, examining the effects of whey proteins, their peptides and amino acids on vascular function and related issues including blood pressure. In addition, it will explore the potential underlying mechanisms responsible for these effects. It concludes that there is increasing evidence that whey proteins, and notably the bioactive peptides and amino acids released during their digestion, can have beneficial effects on aspects of vascular function and thus contribute to CVD risk reduction. It also highlights a number of beneficial effects of whey proteins including those on blood pressure, arterial stiffness, nitric oxide production and inflammation.

Role of whey protein in vascular function: a systematic review and meta-analysis of human intervention studies.

Whey protein (WP) has been heavily appreciated as a rich source of bioactive peptides, with potential benefits for cardiovascular health. This study constitutes a systematic review and meta-analysis summarising the effects of WP consumption on vascular reactivity, arterial stiffness and circulatory biomarkers of vascular function. We searched electronic databases, including PubMed, SCOPUS and Web of science for relevant articles from inception to July 2020. Original clinical trials published in English-language journals that investigated the effects of WP on vascular function were eligible. A total of 720 records were identified in the initial search; from these, sixteen were included in our systematic review and thirteen in meta-analysis. The pooled analysis of six studies showed a significant increase in flow-mediated dilation (FMD) after WP consumption (weighted mean differences (WMD): 1·09 %, 95 % CI: 0·17, 2·01, P= 0·01). Meta-analysis of available data did not show any significant reduction in arterial stiffness measures including augmentation index (effect sizes: 7, WMD: -0·29 %, 95 % CI: -1·58, 0·98, P= 0·64) and pulse wave velocity (effect sizes: 4, WMD: -0·72 m/s, 95 % CI: -1·47, 0·03, P= 0·06). Moreover, the pooled analysis of six effect sizes showed no significant effects on plasma levels of nitric oxide following WP supplementation (WMD: 0·42 μmol/l, 95 % CI: -0·52, 1·36, P= 0·38). The overall results provided evidence supporting a protective effect of WP on endothelial function measured by FMD, but not for arterial stiffness measures and circulatory biomarker of vascular function. Further research is required to substantiate the benefits of WP on vascular function.

Purification and Characterization of Novel Collagen Peptides against Platelet Aggregation and Thrombosis from Salmo salar.

Collagen is a rich source of bioactive peptides and is widely distributed in the skin and bone tissue. In this study, collagen from Salmo salar skin was hydrolyzed with Alcalase or Protamex followed by simulated digestion, YMC ODS-A C18 separation, and ESI-MS/MS analysis. A total of 19 peptides were identified and synthesized for investigation of their antiplatelet activities. Hyp-Gly-Glu-Phe-Gly (OGEFG) and Asp-Glu-Gly-Pro (DEGP) exhibited the most potent activity against ADP-induced platelet aggregation among them with IC50 values of 277.17 and 290.00 μM, respectively, and inhibited the release of β-TG and 5-HT in a dose-dependent manner significantly. Single oral administration of OGEFG and DEGP also inhibited thrombus formation in a ferric chloride-induced arterial thrombosis model at a dose of 200 μmol/kg body weight and did not prolong the bleeding time or cause an immune response in mice. Therefore, our findings indicated that collagen peptides had a potential to be developed into an effective specific medical food in the prevention of thrombotic diseases.

Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs.

Venoms from ants comprise a rich source of bioactive peptides, including antimicrobial peptides. From the proteome and peptidome of the giant ant Dinoponera quadriceps venom, members of five known classes of antimicrobial peptides were disclosed (e.g., dermaseptin-, defensin-, ICK-, pilosulin- and ponericin-like types). Based on comparative analysis, these family members have structural determinants that indicate they could display antimicrobial activities. In previous works, pilosulin- and ponericin-like peptides were demonstrated to be active against bacteria, fungi, and parasites. Herein, the antifungal activity of ponericin- and pilosulin-like peptides were assessed, aiming at the expansion of the knowledge about AMPs in predatory ants and the development of new microbicide strategies to deal with difficult-to-treat fungal infections. Synthetic pilosulin- (Dq-2562, Dq-1503, and Dq-1319) and ponericin-like (Dq-3162) peptides were evaluated for their fungicide and fungistatic activities against different species of Candida, including a drug-resistant clinical strain. The MICs and MLCs were determined for all peptides individually and in combination with general antifungal drugs by the microdilution method. The time-kill kinetic curves were set up by means of a luminescent reagent, of which the light signal is proportional to the number of viable cells. The candicidal synergism observed by the combination of subinhibitory concentrations of peptides and general antimycotic drugs were quantified by the checkerboard test and fluorescent dye permeation assay. The influence of ergosterol on the antifungal activity was verified by supplementation of culture medium. The pilosulin- (Dq-2562 and Dq-1503) and ponericin-like (Dq-3162) were the most active peptides, displaying a broad spectrum of antifungal activity in vitro, with MICs in the range of 0.625 to 10 µM. The combination of peptides and conventional antimycotic drugs displayed a synergistic reduction in the MIC values of individual peptides and drugs, while soluble ergosterol in the culture medium increased the MICs. The fungicide and fungistatic activity of the individual peptides and peptides in combination with antimycotics were time-dependent with a rapid onset of action and long-lasting effect, which involved membrane disruption as an underlying mechanism of their action. Altogether, pilosulin- and ponericin-like peptides from the giant ant D. quadriceps venom display a broad-spectrum of candicidal activity, what allows their inclusion in the row of the antifungal peptides and gives support for further studies on the development of strategies to fight candidiasis.

Purification and cDNA Cloning of Antimicrobial Peptides from the Skin Secretion of the Chinese Frog Rana chensinensis

The skin secretions of amphibians are a rich source of bioactive peptides. We isolated chensirin-1 and chensirin-2 from the skin secretion of the Chinese frog Rana chensinensis. Sephadex-G-50 and RP-HPLC were employed to purify these peptides. The amino acid sequences of these peptides were VLPLVGNLLNDLLGE and IIPLPLGYFAKKT, respectively, as determined by Edman degradation. The molecular weights were 1578.7 and 1460.8 Da, respectively, as analyzed by HPLC-ESI-MS. The chensirin cDNA was cloned by 5′ and 3′ amplification of cDNA ends, synthesized and purified. The antibacterial activities of the chensirins were tested using minimum inhibitory concentration, the results indicated that chensirins inhibit the growth of gram-negative and gram-positive bacteria. Among them, chensirin-1 is a novel peptide with a higher antibacterial activity compared to other similar antimicrobial peptides. These low molecular weight peptides with good antimicrobial efficacy are considered potential sources for developing new antimicrobial agents to improve traditional drug resistance.

Structural Requirement of Casein Peptides for Transcytosis through the Caco-2 Cell Monolayer: Hydrophobicity and Charge Property Affect the Transport Pathway and Efficiency.

Casein is a rich source of bioactive peptides with complete amino acid composition. In this study, the casein peptides identified in our previous study with different hydrophobicities and charge properties were employed to investigate the transport efficiency via the transcytosis pathway across Caco-2 cell monolayers. Results revealed that the apparent permeability coefficient (Papp) values of transcytosis exhibited a linear correlation with a pI of positively charged peptides during bidirectional transport. A similar law was found as for the peptides with different hydrophobicities. The transcytosis route of Pep-II to Pep-VII appears to be the clathrin- and caveolin-independent transcytosis pathway as well as caveolae-mediated transcytosis pathway, showing a linear correlation with Papp values, respectively. Additionally, no direct correlation was shown between the hydrophobicity of peptides and clathrin-mediated transcytosis. Our results help to increase the bioaccessibility of peptide drugs across intestinal mucosa by developing strategies to alter the physicochemical properties without changing bioactivity.

Lactic acid‐mediated isolation of alpha‐, beta‐ and kappa‐casein fractions by isoelectric precipitation coupled with cold extraction from defatted cow milk

The present study focused on the isolation of individual caseins (α, β and κ) from defatted cow's milk using lactic acid‐mediated isoelectric precipitation coupled with cold extraction technique, followed by purification using sucrose‐based density gradient centrifugation method. In vitro characterisation of the isolated casein fractions confirmed preservation of micellar morphology throughout the experimental conditions with anionic surface charge and wider particle size range. The RP‐HPLC analysis showed a peak at retention time of 25.13 min and 27.84 min for α‐casein and β‐casein, respectively. Results confirmed isolation of pure casein fractions from cow's milk which could serve as a rich source of bioactive peptides for nutraceutical/pharmaceutical applications.

Identification of bioactive peptides from brewers’ spent grain and contribution of Leu/Ile to bioactive potency

Abstract Brewer's spent grain (BSG) is a co-product of the brewing industry and is a potentially rich source of bioactive peptides. A BSG protein hydrolysate, manufactured at a semi-pilot scale, mediated significant hypotensive effects 6 h after ingestion in spontaneously hypertensive rats. This hydrolysate was fractionated and further analysed by UPLC-ESI-MS/MS for peptide identification. The peptides, IPY and LPY demonstrated the highest antioxidant activity (0.37 ± 0.02 and 0.34 ± 0.02 µmol Trolox equivalents µM peptide−1, respectively), IPLQP and LPLQP had the highest ACE inhibitory activity (IC50: 3.10 ± 0.60 and 3.17 ± 0.60 µM, respectively) while IPVP had the highest DPP-IV inhibitory activity (IC50: 38.67 ± 5.94 µM). Overall, peptides containing I had higher in vitro bioactivities when compared to peptides having L. Novel BSG peptides were identified with potential for application as naturally derived ingredients for the management of cardiovascular disease and type 2 diabetes.

Rapeseed protein-derived peptides, LY, RALP, and GHS, modulates key enzymes and intermediate products of renin\u2013angiotensin system pathway in spontaneously hypertensive rat

Rapeseed proteins are a rich source of bioactive peptides. LY, RALP and GHS were previously identified from rapeseed protein hydrolysates as potent ACE and renin inhibiting peptides. In this study, the rapeseed peptides were individually evaluated for their molecular mechanisms and regulatory effects on components of the renin–angiotensin system in spontaneously hypertensive rats (SHR), including the mRNA and/or protein levels of angiotensin-converting enzyme (ACE), renin, ACE2, angiotensin II and angiotensin-(1–7) in myocardial tissues. Oral administration of 30 mg peptides/kg body weight every 2 days for five weeks significantly decreased the systolic blood pressure and the myocardial mRNA and protein levels of ACE and renin in SHR. LY, RALP and GHS also increased the expression of ACE2, angiotensin-(1-7) and Mas receptor levels, which may have mediated their antihypertensive activity. Dipeptide LY also inhibited angiotensin II protein expression in the heart tissue. Taken together, the finding demonstrates the multi-target physiological effects of the rapeseed peptides, beyond ACE and renin inhibition, which enhances knowledge of the antihypertensive mechanisms of food protein-derived peptides.