Research

14 pages, 2201 KiB

Open AccessArticle

Alleviating Effects of Black Soybean Peptide on Oxidative Stress Injury Induced by Lead in PC12 Cells via Keap1/Nrf2/TXNIP Signaling Pathway

by Ning Li, Liuding Wen, Tiange Li, Huijie Yang, Mingwu Qiao, Tianlin Wang, Lianjun Song, Xianqing Huang, Mingming Li, Erkigul Bukyei and Fangyu Wang

Nutrients 2022, 14(15), 3102; https://doi.org/10.3390/nu14153102 - 28 Jul 2022

Cited by 6 | Viewed by 1940

Abstract

Many researchers have found that Pb exposure can cause oxidative stress damage to the body’s tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage [...] Read more.

Many researchers have found that Pb exposure can cause oxidative stress damage to the body’s tissue. Black soybean peptide (BSP) has a variety of physiological functions, especially in terms of oxidative stress. Nevertheless, the mitigation function of BSPs on Pb-induced oxidative stress damage in PC12 cells has not been clearly defined. In this study, cell viability was detected by CCK8. Oxidative stress indicators, such as ROS, GSH/GSSG, MDA, SOD, CAT, GPx, and GR, were tested with biochemical kit. Protein expression of Keap1, Nrf2, and TXNIP was measured by Western blot. Compared with the control group, Pb reduced the cell viability of PC12 cells. However, BSP treatment significantly increased the viability of PC12 cells induced by lead exposure (p < 0.05). Lead can enrich the contents of MDA and ROS, but decrease the amount of CAT, SOD, GR, GPx, and GSH/GSSG in PC12 cells, while BSP can alleviate it (p < 0.05). Lead can enhance the expression of Keap1 and TXNIP proteins, but reduce Nrf2 expression. In contrast, BSPs reversed this phenomenon (p < 0.05). BSPs can alleviate oxidative stress injury induced by lead in PC12 cells through the Keap1/Nrf2/TXNIP signaling pathway. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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9 pages, 2055 KiB

Open AccessArticle

Assessment of the Cholesterol-Lowering Effect of MOMAST^®: Biochemical and Cellular Studies

by Martina Bartolomei, Carlotta Bollati, Jianqiang Li, Anna Arnoldi and Carmen Lammi

Nutrients 2022, 14(3), 493; https://doi.org/10.3390/nu14030493 - 23 Jan 2022

Cited by 4 | Viewed by 2728

Abstract

MOMAST^® is a patented phenolic complex derived from the olive oil vegetation water, a by-product of the olive oil supply chain, in which hydroxytyrosol (OH-Tyr) and tyrosol (Tyr) and verbascoside are the main compounds. This study was aimed at investigating its hypocholesterolemic [...] Read more.

MOMAST^® is a patented phenolic complex derived from the olive oil vegetation water, a by-product of the olive oil supply chain, in which hydroxytyrosol (OH-Tyr) and tyrosol (Tyr) and verbascoside are the main compounds. This study was aimed at investigating its hypocholesterolemic effect by assessing the ability to modulate the low-density lipoprotein (LDL) receptor (LDLR)/sterol regulatory element-binding protein 2 (SREBP-2), and proprotein convertase subtilisin/kexin type 9 (PCSK9) pathways. MOMAST^® inhibits the in vitro activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGC_OAR) with a dose-response trend. After the treatment of HepG2 cells, MOMAST^® increases the SREBP-2, LDLR, and HMGCoAR protein levels leading, from a functional point of view to an improved ability of hepatic cells to up-take LDL from the extracellular environment with a final cholesterol-lowering effect. Furthermore, MOMAST^® decreased the PCSK9 protein levels and its secretion in the extracellular environment, presumably via the reduction of the hepatic nuclear factor 1-α (HNF1-α). The experiments were performed in parallel, using pravastatin as a reference compound. Results demonstrated that MOMAST^® may be exploited as a new ingredient for the development of functional foods and/or nutraceuticals for cardiovascular disease prevention. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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15 pages, 1541 KiB

Open AccessArticle

Beneficial Impact of Pork Dry-Cured Ham Consumption on Blood Pressure and Cardiometabolic Markers in Individuals with Cardiovascular Risk

by Silvia Montoro-García, Ángeles Velasco-Soria, Leticia Mora, Carmen Carazo-Díaz, David Prieto-Merino, Antonio Avellaneda, Domingo Miranzo, Teresa Casas-Pina, Fidel Toldrá and José Abellán-Alemán

Nutrients 2022, 14(2), 298; https://doi.org/10.3390/nu14020298 - 11 Jan 2022

Cited by 8 | Viewed by 3455

Abstract

Background: Evidence suggests that bioactive peptides reduce hypertension and affect certain metabolic pathways. Methods: Fifty-four volunteers with stage 1 prehypertension and/or hypercholesterolemia and/or basal glucose >100 mg/dL were recruited and randomized to pork dry-cured ham (n = 35) or cooked ham (placebo [...] Read more.

Background: Evidence suggests that bioactive peptides reduce hypertension and affect certain metabolic pathways. Methods: Fifty-four volunteers with stage 1 prehypertension and/or hypercholesterolemia and/or basal glucose >100 mg/dL were recruited and randomized to pork dry-cured ham (n = 35) or cooked ham (placebo group; n = 19) for 28 days. After a wash-out period, meat products were changed for 28 additional days. Bioactive peptides composition and enzyme inhibitory activities of both products were characterized. Treatment comparisons for the main effects were made using a two (treatment) × two (times) repeated measures minus the effect of cooked ham (placebo). Results: 24 h mean systolic and diastolic pressures decreased up to 2.4 mmHg in the dry-cured ham period (treatment effect, p = 0.0382 y p = 0.0233, respectively) as well as the number of systolic pressure measures > 135 mmHg (treatment effect, p = 0.0070). Total cholesterol levels also decreased significantly after dry-cured ham intake (p = 0.049). No significant differences were observed between the two treatments for basal glucose, HOMA-IR index and insulin levels (p > 0.05). However, a significant rise of ghrelin levels was observed (treatment effect, p = 0.0350), while leptin plasma values slightly decreased (treatment effect, p = 0.0628). Conclusions: This study suggested the beneficial effects of regular dry-cured ham consumption on the improvement of systolic/diastolic blood pressures and facilitated the maintenance of metabolic pathways, which may be beneficial in the primary prevention of cardiovascular disease. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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10 pages, 1027 KiB

Open AccessArticle

Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

by Chiara Macchi, Maria Francesca Greco, Nicola Ferri, Paolo Magni, Anna Arnoldi, Alberto Corsini, Cesare R. Sirtori, Massimiliano Ruscica and Carmen Lammi

Nutrients 2022, 14(1), 193; https://doi.org/10.3390/nu14010193 - 31 Dec 2021

Cited by 9 | Viewed by 1970

Abstract

Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods, the hypocholesterolemic properties of soy are driven by a [...] Read more.

Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods, the hypocholesterolemic properties of soy are driven by a stimulation of LDL-receptor (LDL-R) activity. Aim: To characterize the effect of two soy peptides, namely, β-conglycinin-derived YVVNPDNDEN and YVVNPDNNEN on the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key-regulators of the LDL-R. Methods: PCSK9 promoter activity (luciferase assay), PCSK9 protein expression (WB) and secretion (ELISA), PCSK9 interaction with LDL-R (binding assay) and human HepG2 cells were the objects of this investigation. Results: Treatment with YVVNPDNNEN peptide has led to a rise in PCSK9 gene expression (90.8%) and transcriptional activity (86.4%), and to a decrement in PCSK9 intracellular and secreted protein (−42.9%) levels. YVVNPDNNEN peptide reduced the protein expression of transcriptional factor HNF1α. Most changes driven by YVVNPDNDEN peptide were not statistically significant. Neither peptide inhibited the PCSK9–LDLR interaction. Conclusions: Although sharing a common effect on LDL-R levels through the inhibition of 3-hydroxy-3-methylglutaryl CoA reductase activity, only the YVVNPDNNEN peptide has an additional mechanism via the downregulation of PCSK9 protein levels. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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16 pages, 2547 KiB

Open AccessArticle

Anti-Salmonella Activity and Peptidomic Profiling of Peptide Fractions Produced from Sturgeon Fish Skin Collagen (Huso huso) Using Commercial Enzymes

by Maryam Atef, Yasmina Ait Chait, Seyed Mahdi Ojagh, Ali Mohammad Latifi, Mina Esmaeili, Riadh Hammami and Chibuike C. Udenigwe

Nutrients 2021, 13(8), 2657; https://doi.org/10.3390/nu13082657 - 30 Jul 2021

Cited by 13 | Viewed by 3134

Abstract

This study investigated peptide fractions from fish skin collagen for antibacterial activity against Escherichia coli and Salmonella strains. The collagen was hydrolyzed with six commercial proteases, including trypsin, Alcalase, Neutrase, Flavourzyme, pepsin and papain. Hydrolyzed samples obtained with trypsin and Alcalase had the [...] Read more.

This study investigated peptide fractions from fish skin collagen for antibacterial activity against Escherichia coli and Salmonella strains. The collagen was hydrolyzed with six commercial proteases, including trypsin, Alcalase, Neutrase, Flavourzyme, pepsin and papain. Hydrolyzed samples obtained with trypsin and Alcalase had the largest number of small peptides (molecular weight <10 kDa), while the hydrolysate produced with papain showed the lowest degree of hydrolysis and highest number of large peptides. Four hydrolysates were found to inhibit the growth of the Gram-negative bacteria, with papain hydrolysate showing the best activity against E. coli, and Neutrase and papain hydrolysates showing the best activity against S. abony; hydrolysates produced with trypsin and pepsin did not show detectable antibacterial activity. After acetone fractionation of the latter hydrolysates, the peptide fractions demonstrated enhanced dose-dependent inhibition of the growth (colony-forming units) of four Salmonella strains, including S. abony (NCTC 6017), S. typhimurium (ATCC 13311), S. typhimurium (ATCC 14028) and S. chol (ATCC 10708). Shotgun peptidomics analysis of the acetone fractions of Neutrase and papain hydrolysates resulted in the identification of 71 and 103 peptides, respectively, with chain lengths of 6–22 and 6–24, respectively. This work provided an array of peptide sequences from fish skin collagen for pharmacophore identification, structure–activity relationship studies, and further investigation as food-based antibacterial agents against pathogenic microorganisms. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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14 pages, 2316 KiB

Open AccessArticle

Anti-Obesity and Hypocholesterolemic Actions of Protamine-Derived Peptide RPR (Arg-Pro-Arg) and Protamine in High-Fat Diet-Induced C57BL/6J Mice

by Maihemuti Mijiti, Ryosuke Mori, Bingyu Huang, Kenichiro Tsukamoto, Keisuke Kiriyama, Keita Sutoh and Satoshi Nagaoka

Nutrients 2021, 13(8), 2501; https://doi.org/10.3390/nu13082501 - 22 Jul 2021

Cited by 9 | Viewed by 2897

Abstract

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 [...] Read more.

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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16 pages, 20192 KiB

Open AccessArticle

Protective Effects of Small-Molecule Oligopeptides Isolated from Tilapia Fish Scale on Ethanol-Induced Gastroduodenal Injury in Rats

by Jiani Hu, Rui Liu, Xiaochen Yu, Zhen Li, Xinran Liu, Yuntao Hao, Na Zhu, Jiawei Kang and Yong Li

Nutrients 2021, 13(6), 2078; https://doi.org/10.3390/nu13062078 - 17 Jun 2021

Cited by 9 | Viewed by 2346

Abstract

Peptic ulcer has a serious impact on people’s health around the world, and traditional medicines can cause adverse reactions. This study investigated the protective effects of tilapia collagen oligopeptides (TCOPs) on gastroduodenal injury. Seventy-two specific pathogen-free (SPF) male Sprague Dawley (SD) rats were [...] Read more.

Peptic ulcer has a serious impact on people’s health around the world, and traditional medicines can cause adverse reactions. This study investigated the protective effects of tilapia collagen oligopeptides (TCOPs) on gastroduodenal injury. Seventy-two specific pathogen-free (SPF) male Sprague Dawley (SD) rats were randomly divided into six groups according to body weight: normal control group, ethanol group, whey protein group (500 mg/kg BW), and three TCOPs dose groups (250, 500, 1000 mg/kg BW). After intragastric administration for 30 days, the acute gastroduodenal injury was induced by anhydrous ethanol (5 mL/kg, intragastrically) in all groups except the normal control group. Biomarkers in gastric and duodenal tissue and serum were measured. Furthermore, western blot was used to detect the expression of apoptosis-related proteins. The results showed that the administration with TCOPs significantly reduced gastric and duodenal ulcer index, increased gastric juice pH, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, along with the reduction of malondialdehyde (MDA) contents. TCOPs decreased tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and myeloperoxidase (MPO) levels, while interleukin– 10 (IL-10) levels were increased. Furthermore, pepsinogens 1 (PG1), pepsinogens 2 (PG2), gastrin (GAS), and the pepsinogen ratio (PGR) were decreased, the prostaglandin E2 (PGE2) and NO contents were increased after TCOPs intervention. Moreover, TCOPs up-regulated the expression of Bcl-2 and inhibited the expression of Bax and Caspase-3. In conclusion, TCOPs have protective effects on ethanol-induced gastroduodenal injury through gastrointestinal mucosal microcirculation promotion, antioxidation, anti-inflammation, and anti-apoptosis mechanisms. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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14 pages, 4290 KiB

Open AccessArticle

Investigation of Chlorella pyrenoidosa Protein as a Source of Novel Angiotensin I-Converting Enzyme (ACE) and Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides

by Yuchen Li, Gilda Aiello, Enrico Mario Alessandro Fassi, Giovanna Boschin, Martina Bartolomei, Carlotta Bollati, Gabriella Roda, Anna Arnoldi, Giovanni Grazioso and Carmen Lammi

Nutrients 2021, 13(5), 1624; https://doi.org/10.3390/nu13051624 - 12 May 2021

Cited by 17 | Viewed by 3422

Abstract

Chlorella pyrenoidosa (C. pyrenoidosa) is a microalgae species with a remarkably high protein content that may potentially become a source of hypotensive and hypoglycemic peptides. In this study, C. pyrenoidosa proteins were extracted and hydrolyzed overnight with pepsin and trypsin with [...] Read more.

Chlorella pyrenoidosa (C. pyrenoidosa) is a microalgae species with a remarkably high protein content that may potentially become a source of hypotensive and hypoglycemic peptides. In this study, C. pyrenoidosa proteins were extracted and hydrolyzed overnight with pepsin and trypsin with final degrees of hydrolysis of 18.7% and 35.5%, respectively. By LC-MS/MS, 47 valid peptides were identified in the peptic hydrolysate (CP) and 66 in the tryptic one (CT). At the concentration of 1.0 mg/mL, CP and CT hydrolysates inhibit in vitro the angiotensin-converting enzyme (ACE) activity by 84.2 ± 0.37% and 78.6 ± 1.7%, respectively, whereas, tested at cellular level at the concentration of 5.0 mg/mL, they reduce the ACE activity by 61.5 ± 7.7% and 69.9 ± 0.8%, respectively. At the concentration of 5.0 mg/mL, they decrease in vitro the DPP-IV activity by 63.7% and 69.6% and in Caco-2 cells by 38.4% and 42.5%, respectively. Short peptides (≤10 amino acids) were selected for investigating the potential interaction with ACE and DPP-IV by using molecular modeling approaches and four peptides were predicted to block both enzymes. Finally, the stability of these peptides was investigated against gastrointestinal digestion. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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14 pages, 2947 KiB

Open AccessArticle

Potential Health Benefits Associated with Lunasin Concentration in Dietary Supplements and Lunasin-Enriched Soy Extract

by Elvira Gonzalez de Mejia, Erick Damian Castañeda-Reyes, Luis Mojica, Vermont Dia, Hui Wang, Toni Wang and Lawrence A. Johnson

Nutrients 2021, 13(5), 1618; https://doi.org/10.3390/nu13051618 - 12 May 2021

Cited by 10 | Viewed by 3066

Abstract

Lunasin has demonstrated antioxidative, anti-inflammatory, and chemopreventive properties. The objectives were to evaluate the concentration of lunasin in different lunasin-based commercial dietary supplements, to produce a lunasin-enriched soy extract (LESE) using a two-step pilot-plant-based ultrafiltration process, and to evaluate their biological potential in [...] Read more.

Lunasin has demonstrated antioxidative, anti-inflammatory, and chemopreventive properties. The objectives were to evaluate the concentration of lunasin in different lunasin-based commercial dietary supplements, to produce a lunasin-enriched soy extract (LESE) using a two-step pilot-plant-based ultrafiltration process, and to evaluate their biological potential in vitro. LESE was produced using 30 and 1 kDa membranes in a custom-made ultrafiltration skid. Lunasin was quantified in eight products and LESE. Lunasin concentrations of the lunasin-based products ranged from 9.2 ± 0.6 to 25.7 ± 1.1 mg lunasin/g protein. The LESE extract contained 58.2 mg lunasin/g protein, up to 6.3-fold higher lunasin enrichment than lunasin-based dietary supplements. Antioxidant capacity ranged from 121.5 mmol Trolox equivalents (TE)/g in Now^® Kids to 354.4 mmol TE/g in LESE. Histone acetyltransferase (HAT) inhibition ranged from 5.3% on Soy Sentials^® to 38.3% on synthetic lunasin. ORAC and lunasin concentrations were positively correlated, and HAT and lunasin concentrations were negatively correlated (p < 0.05). Melanoma B16-F10 and A375 cells treated with lunasin showed dose-dependent inhibitory potential (IC₅₀ equivalent to 330 and 370 μM lunasin, respectively). Lunasin showed protein kinase B expression (57 ± 14%) compared to the control (100%) in B16-F10. Lunasin concentration found in commercial products and lunasin-enriched soy extract could exert benefits to consumers. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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12 pages, 2156 KiB

Open AccessArticle

Transport of Dietary Anti-Inflammatory Peptide, γ-Glutamyl Valine (γ-EV), across the Intestinal Caco-2 Monolayer

by Snigdha Guha, Sophie Alvarez and Kaustav Majumder

Nutrients 2021, 13(5), 1448; https://doi.org/10.3390/nu13051448 - 24 Apr 2021

Cited by 22 | Viewed by 4132

Abstract

The present study analyzed the transepithelial transport of the dietary anti-inflammatory peptide, γ-glutamyl valine (γ-EV). γ-EV is naturally found in dry edible beans. Our previous study demonstrated the anti-inflammatory potency of γ-EV against vascular inflammation at a concentration of 1mM, and that it [...] Read more.

The present study analyzed the transepithelial transport of the dietary anti-inflammatory peptide, γ-glutamyl valine (γ-EV). γ-EV is naturally found in dry edible beans. Our previous study demonstrated the anti-inflammatory potency of γ-EV against vascular inflammation at a concentration of 1mM, and that it can transport with the apparent permeability coefficient (P_app) of 1.56 × 10⁻⁶ ± 0.7 × 10⁻⁶ cm/s across the intestinal Caco-2 cells. The purpose of the current study was to explore whether the permeability of the peptide could be enhanced and to elucidate the mechanism of transport of γ-EV across Caco-2 cells. The initial results indicated that γ-EV was nontoxic to the Caco-2 cells up to 5 mM concentration and could be transported across the intestinal cells intact. During apical-to-basolateral transport, a higher peptide dose (5 mM) significantly (p < 0.01) enhanced the transport rate to 2.5 × 10⁻⁶ ± 0.6 × 10⁻⁶ cm/s. Cytochalasin-D disintegrated the tight-junction proteins of the Caco-2 monolayer and increased the P_app of γ-EV to 4.36 × 10⁻⁶ ± 0.16 × 10⁻⁶ cm/s (p < 0.001), while theaflavin 3′-gallate and Gly-Sar significantly decreased the P_app (p < 0.05), with wortmannin having no effects on the peptide transport, indicating that the transport route of γ-EV could be via both PepT1-mediated and paracellular. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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17 pages, 2295 KiB

Open AccessArticle

Trans-Epithelial Transport, Metabolism, and Biological Activity Assessment of the Multi-Target Lupin Peptide LILPKHSDAD (P5) and Its Metabolite LPKHSDAD (P5-Met)

by Carmen Lammi, Gilda Aiello, Carlotta Bollati, Jianqiang Li, Martina Bartolomei, Giulia Ranaldi, Simonetta Ferruzza, Enrico Mario Alessandro Fassi, Giovanni Grazioso, Yula Sambuy and Anna Arnoldi

Nutrients 2021, 13(3), 863; https://doi.org/10.3390/nu13030863 - 05 Mar 2021

Cited by 17 | Viewed by 2612

Abstract

P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases [...] Read more.

P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5-frag) and LPKHSDAD (P5-met), and that both P5 and P5-met are linearly absorbed by differentiated human intestinal Caco-2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5-met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi-target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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17 pages, 6282 KiB

Open AccessArticle

Radioprotective Effect of Whey Hydrolysate Peptides against γ-Radiation-Induced Oxidative Stress in BALB/c Mice

by Xin-Ran Liu, Na Zhu, Yun-Tao Hao, Xiao-Chen Yu, Zhen Li, Rui-Xue Mao, Rui Liu, Jia-Wei Kang, Jia-Ni Hu and Yong Li

Nutrients 2021, 13(3), 816; https://doi.org/10.3390/nu13030816 - 02 Mar 2021

Cited by 9 | Viewed by 2430

Abstract

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of [...] Read more.

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against ⁶⁰Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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16 pages, 1603 KiB

Open AccessArticle

Identification and Comparison of Peptides from Chickpea Protein Hydrolysates Using Either Bromelain or Gastrointestinal Enzymes and Their Relationship with Markers of Type 2 Diabetes and Bitterness

by Subhiksha Chandrasekaran, Diego Luna-Vital and Elvira Gonzalez de Mejia

Nutrients 2020, 12(12), 3843; https://doi.org/10.3390/nu12123843 - 16 Dec 2020

Cited by 35 | Viewed by 4580

Abstract

The chickpea (Cicer arietinum L.) is one of the most important pulses worldwide. The objective was to identify, compare and evaluate peptides from chickpea hydrolysates produced by two enzymatic treatments. The antidiabetic potential and bitterness of the peptides and induction of bitter [...] Read more.

The chickpea (Cicer arietinum L.) is one of the most important pulses worldwide. The objective was to identify, compare and evaluate peptides from chickpea hydrolysates produced by two enzymatic treatments. The antidiabetic potential and bitterness of the peptides and induction of bitter receptors were identified in silico. Proteins were isolated from the Kabuli variety. Peptides were produced from the proteins using a simulated digestive system (pepsin/pancreatin, 1:50 Enzyme/Protein, E/P), and these peptides were compared with those produced via bromelain hydrolysis (1:50 E/P). The protein profiles, sequences and characteristics of the peptides were evaluated. The biochemical inhibition and molecular docking of dipeptidyl peptidase-IV (DPP-IV), α-amylase and α-glucosidase were also studied. The molecular docking identified peptides from enzymatic hydrolysis as inhibitors of DPP-IV. The high hydrophobicity of the peptides indicated the potential for bitterness. There was no correlation between peptide length and DPP-IV binding. Peptides sequenced from the pepsin/pancreatin hydrolysates, PHPATSGGGL and YVDGSGTPLT, had greater affinity for the DPP-IV catalytic site than the peptides from the bromelain hydrolysates. These results are in agreement with their biochemical inhibition, when considering the inhibition of sitagliptin (54.3 µg/mL) as a standard. The bitter receptors hTAS2R38, hTAS2R5, hTAS2R7 and hTAS2R14 were stimulated by most sequences, which could be beneficial in the treatment of type 2 diabetes. Chickpea hydrolysates could be utilized as functional ingredients to be included in the diet for the prevention of diabetes. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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16 pages, 1574 KiB

Open AccessArticle

Identification and Characterization of Edible Cricket Peptides on Hypertensive and Glycemic In Vitro Inhibition and Their Anti-Inflammatory Activity on RAW 264.7 Macrophage Cells

by Felicia Hall, Lavanya Reddivari and Andrea M. Liceaga

Nutrients 2020, 12(11), 3588; https://doi.org/10.3390/nu12113588 - 23 Nov 2020

Cited by 38 | Viewed by 4124

Abstract

Recent studies continue to demonstrate the potential of edible insects as a protein base to obtain bioactive peptides applicable for functional food development. This study aimed at identifying antihypertensive, anti-glycemic, and anti-inflammatory peptides derived from the in vitro gastrointestinal digests of cricket protein [...] Read more.

Recent studies continue to demonstrate the potential of edible insects as a protein base to obtain bioactive peptides applicable for functional food development. This study aimed at identifying antihypertensive, anti-glycemic, and anti-inflammatory peptides derived from the in vitro gastrointestinal digests of cricket protein hydrolysates. After sequential fractionation, the protein digest subfraction containing the lowest molecular weight (<0.5 kDa), hydrophobic (C18) and cationic peptides (IEX) was found responsible for the most bioactivity. The cationic peptide fraction significantly reduced (p < 0.05) α-amylase, α-glucosidase, and angiotensin converting enzyme (ACE) activity in vitro, and also inhibited the expression of NF-κB in RAW 264.7 macrophage cells. A total of 28 peptides were identified with mass spectrometry (LC–MS/MS) and de novo sequencing from the potent fraction. Three novel peptides YKPRP, PHGAP, and VGPPQ were chosen for the molecular docking studies. PHGAP and VGPPQ exhibited a higher degree of non-covalent interactions with the enzyme active site residues and binding energies comparable to captopril. Results from this study demonstrate the bioactive potential of edible cricket peptides, especially as ACE inhibitors. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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13 pages, 1458 KiB

Open AccessArticle

Phosvitin Derived Phospho-Peptides Show Better Osteogenic Potential than Intact Phosvitin in MC3T3-E1 Osteoblastic Cells

by Subhadeep Chakrabarti, Jiandong Ren and Jianping Wu

Nutrients 2020, 12(10), 2998; https://doi.org/10.3390/nu12102998 - 30 Sep 2020

Cited by 10 | Viewed by 2673

Abstract

Phosphorylated proteins from food sources have been investigated as regulators of bone formation with potential benefits in treating osteoporosis. Egg, a cheap and nutritious food, is also the source of various proteins and bioactive peptides with applications in human health. Egg yolk is [...] Read more.

Phosphorylated proteins from food sources have been investigated as regulators of bone formation with potential benefits in treating osteoporosis. Egg, a cheap and nutritious food, is also the source of various proteins and bioactive peptides with applications in human health. Egg yolk is rich in phosvitin, the most phosphorylated protein in nature. Phosvitin has been shown to improve bone health in experimental animals, although the molecular mechanisms and its specific effects on bone-forming osteoblastic cells are incompletely understood. Previous work in our group has identified pancreatin-generated phosvitin phospho-peptides (PPP) as a potential source for bioactive peptides. Given this background, we examined the roles of both phosvitin and PPP in the function of osteoblastic cells. Our results demonstrated their potential to improve bone health by promoting osteoblast differentiation and proliferation, suppressing osteoclast recruitment and the deposition of extracellular matrix, although PPP appeared to demonstrate superior osteogenic functions compared to phosvitin alone. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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24 pages, 4551 KiB

Open AccessArticle

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

by Diana Reyes-Pavón, Daniel Cervantes-García, Luis G. Bermúdez-Humarán, Laura Elena Córdova-Dávalos, Andrés Quintanar-Stephano, Mariela Jiménez and Eva Salinas

Nutrients 2020, 12(10), 2942; https://doi.org/10.3390/nu12102942 - 25 Sep 2020

Cited by 13 | Viewed by 3182

Abstract

Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic [...] Read more.

Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic activity of GMP was evaluated using a rat ovalbumin (OVA)-induced FA model with gastrointestinal manifestation. Rats were orally GMP treated from 3 days prior and during FA development. The severity of food anaphylaxis and diarrheal episodes, antibody production and histamine level were measured. Histopathological changes, inflammation and predominant cytokine profile at intestine were analyzed. Oral GMP intake decreased clinical signs and diarrhea severity induced by allergen, with a significant reduction in intestinal edema and expression level of IL-1β and TNF-α. Prophylaxis with GMP also diminished serum anti-OVA IgE and IgG1, and histamine levels. GMP treatment markedly decreased eosinophil infiltration, mast cell and goblet cell hyperplasia, total IgE expression in intestine, and prevented histological changes in villi, crypts and internal muscularis layer. The treatment effectively suppressed IL-5, IL-13 and GATA3 expression and skewed the intestinal cytokine profile toward type 1 and regulatory. These results suggest that GMP may protect against FA through down-regulating the type 2 inflammatory response. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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18 pages, 3084 KiB

Open AccessArticle

IIAEK Targets Intestinal Alkaline Phosphatase (IAP) to Improve Cholesterol Metabolism with a Specific Activation of IAP and Downregulation of ABCA1

by Asahi Takeuchi, Kentaro Hisamatsu, Natsuki Okumura, Yuki Sugimitsu, Emiko Yanase, Yoshihito Ueno and Satoshi Nagaoka

Nutrients 2020, 12(9), 2859; https://doi.org/10.3390/nu12092859 - 18 Sep 2020

Cited by 14 | Viewed by 4032

Abstract

IIAEK (Ile-Ile-Ala-Glu-Lys, lactostatin) is a novel cholesterol-lowering pentapeptide derived from bovine milk β-lactoglobulin. However, the molecular mechanisms underlying the IIAEK-mediated suppression of intestinal cholesterol absorption are unknown. Therefore, we evaluated the effects of IIAEK on intestinal cholesterol metabolism in a human intestinal model [...] Read more.

IIAEK (Ile-Ile-Ala-Glu-Lys, lactostatin) is a novel cholesterol-lowering pentapeptide derived from bovine milk β-lactoglobulin. However, the molecular mechanisms underlying the IIAEK-mediated suppression of intestinal cholesterol absorption are unknown. Therefore, we evaluated the effects of IIAEK on intestinal cholesterol metabolism in a human intestinal model using Caco-2 cells. We found that IIAEK significantly reduced the expression of intestinal cholesterol metabolism-associated genes, particularly that of the ATP-binding cassette transporter A1 (ABCA1). Subsequently, we chemically synthesized a novel molecular probe, IIXEK, which can visualize a complex of target proteins interacting with photoaffinity-labeled IIAEK by fluorescent substances. Through photoaffinity labeling and MS analysis with IIXEK for the rat small intestinal mucosa and intestinal lipid raft fractions of Caco-2 cells, we identified intestinal alkaline phosphatase (IAP) as a specific molecule interacting with IIAEK and discovered the common IIAEK-binding amino acid sequence, GFYLFVEGGR. IIAEK significantly increased IAP mRNA and protein levels while decreasing ABCA1 mRNA and protein levels in Caco-2 cells. In conclusion, we found that IIAEK targets IAP to improve cholesterol metabolism via a novel signaling pathway involving the specific activation of IAP and downregulation of intestinal ABCA1. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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12 pages, 1166 KiB

Open AccessArticle

Immunomodulatory and Antioxidant Properties of Wheat Gluten Protein Hydrolysates in Human Peripheral Blood Mononuclear Cells

by Ivan Cruz-Chamorro, Nuria Álvarez-Sánchez, Guillermo Santos-Sánchez, Justo Pedroche, María-Soledad Fernández-Pachón, Francisco Millán, María Carmen Millán-Linares, Patricia Judith Lardone, Ignacio Bejarano, Juan Miguel Guerrero and Antonio Carrillo-Vico

Nutrients 2020, 12(6), 1673; https://doi.org/10.3390/nu12061673 - 04 Jun 2020

Cited by 20 | Viewed by 4403

Abstract

Peptides from several plant food proteins not only maintain the nutritional values of the original protein and decrease the environmental impact of animal agriculture, but also exert biological activities with significant health-beneficial effects. Wheat is the most important food grain source in the [...] Read more.

Peptides from several plant food proteins not only maintain the nutritional values of the original protein and decrease the environmental impact of animal agriculture, but also exert biological activities with significant health-beneficial effects. Wheat is the most important food grain source in the world. However, negative attention on wheat-based products has arose due to the role of gluten in celiac disease. A controlled enzymatic hydrolysis could reduce the antigenicity of wheat gluten protein hydrolysates (WGPHs). Therefore, the aims of the present study were to evaluate the effects of the in vitro administration of Alcalase-generated WGPHs on the immunological and antioxidant responses of human peripheral blood mononuclear cells (PBMCs) from 39 healthy subjects. WGPH treatment reduced cell proliferation and the production of the Type 1 T helper (Th1) and Th17 pro-inflammatory cytokines IFN-γ and IL-17, respectively. WPGHs also improved the cellular anti-inflammatory microenvironment, increasing Th2/Th1 and Th2/Th17 balances. Additionally, WGPHs improved global antioxidant capacity, increased levels of the reduced form of glutathione and reduced nitric oxide production. These findings, not previously reported, highlight the beneficial capacity of these vegetable protein hydrolysates, which might represent an effective alternative in functional food generation. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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16 pages, 4825 KiB

Open AccessArticle

A Novel Peptide Oligomer of Bacitracin Induces M1 Macrophage Polarization by Facilitating Ca²⁺ Influx

by Seon Yeong Ji, Hyesook Lee, Hyun Hwangbo, Su-Hyun Hong, Hee-Jae Cha, Cheol Park, Do-Hyung Kim, Gi-Young Kim, Suhkmann Kim, Heui-Soo Kim, Jin Cheol Yoo and Yung Hyun Choi

Nutrients 2020, 12(6), 1603; https://doi.org/10.3390/nu12061603 - 29 May 2020

Cited by 16 | Viewed by 3002

Abstract

Antimicrobial peptides (AMPs) are components of the innate immune system and form the first defense against pathogens for various organisms. In the present study, we assessed whether CSP32, a novel AMP oligomer of bacitracin isolated from a strain of Bacillus spp., regulates the [...] Read more.

Antimicrobial peptides (AMPs) are components of the innate immune system and form the first defense against pathogens for various organisms. In the present study, we assessed whether CSP32, a novel AMP oligomer of bacitracin isolated from a strain of Bacillus spp., regulates the polarization of murine macrophage-like RAW 264.7 cells. CSP32 stimulated phagocytosis while inducing the appearance of the typical M1 polarized macrophage phenotype; these M1 macrophages play a role in host defense against pathogens. Furthermore, our results showed that CSP32 enhanced the expression and production of pro-inflammatory mediators, such as cytokines and chemokines. In addition, the CSP32-stimulated inflammatory mediators were induced mainly by the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) signaling pathway during M1 macrophage polarization. In particular, CSP32 markedly increased the numbers of Ca²⁺-positive macrophages while upregulating phospholipase C and activating protein kinase Cε. Furthermore, the inhibition of intracellular Ca²⁺ by BAPTA-AM, a Ca²⁺ chelator, significantly suppressed the CSP32-mediated phagocytosis, inflammatory mediator production, and NF-κB activation. In conclusion, our data suggested that CSP32-stimulated M1 macrophage polarization is dependent on the calcium signaling pathway and may result in enhanced immune capacities. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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11 pages, 1284 KiB

Open AccessArticle

Phycobiliproteins from Arthrospira Platensis (Spirulina): A New Source of Peptides with Dipeptidyl Peptidase-IV Inhibitory Activity

by Yuchen Li, Gilda Aiello, Carlotta Bollati, Martina Bartolomei, Anna Arnoldi and Carmen Lammi

Nutrients 2020, 12(3), 794; https://doi.org/10.3390/nu12030794 - 18 Mar 2020

Cited by 44 | Viewed by 4196

Abstract

Arthrospira platensis (spirulina) is a cyanobacterium, which contains mainly two phycobiliproteins (PBP), i.e., C-phycocyanin (C-PC) and allophycocyanin (APC). In this study, PBP were hydrolyzed using trypsin, and the composition of the hydrolysate was characterized by HPLC-ESI-MS/MS. Furthermore, the potential anti-diabetic activity was assessed [...] Read more.

Arthrospira platensis (spirulina) is a cyanobacterium, which contains mainly two phycobiliproteins (PBP), i.e., C-phycocyanin (C-PC) and allophycocyanin (APC). In this study, PBP were hydrolyzed using trypsin, and the composition of the hydrolysate was characterized by HPLC-ESI-MS/MS. Furthermore, the potential anti-diabetic activity was assessed by using either biochemical or cellular techniques. Findings suggest that PBP peptides inhibit DPP-IV activity in vitro with a dose-response trend and an IC₅₀ value falling in the range between 0.5 and 1.0 mg/mL. A lower inhibition of the DPP-IV activity expressed by Caco-2 cells was observed, which was explained by a secondary metabolic degradation exerted by the same cells. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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Review

Jump to: Research, Other

18 pages, 532 KiB

Open AccessReview

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

by Innocent U. Okagu, Joseph C. Ndefo, Emmanuel C. Aham, Joy I. Obeme-Nmom, Precious E. Agboinghale, Rita N. Aguchem, Regina N. Nechi and Carmen Lammi

Nutrients 2021, 13(9), 3266; https://doi.org/10.3390/nu13093266 - 18 Sep 2021

Cited by 25 | Viewed by 4618

Abstract

There is a renewed interest on the reliance of food-based bioactive compounds as sources of nutritive factors and health-beneficial chemical compounds. Among these food components, several proteins from foods have been shown to promote health and wellness as seen in proteins such as [...] Read more.

There is a renewed interest on the reliance of food-based bioactive compounds as sources of nutritive factors and health-beneficial chemical compounds. Among these food components, several proteins from foods have been shown to promote health and wellness as seen in proteins such as α/γ-conglutins from the seeds of Lupinus species (Lupin), a genus of leguminous plant that are widely used in traditional medicine for treating chronic diseases. Lupin-derived peptides (LDPs) are increasingly being explored and they have been shown to possess multifunctional health improving properties. This paper discusses the intestinal transport, bioavailability and biological activities of LDPs, focusing on molecular mechanisms of action as reported in in vitro, cell culture, animal and human studies. The potentials of several LDPs to demonstrate multitarget mechanism of regulation of glucose and lipid metabolism, chemo- and osteoprotective properties, and antioxidant and anti-inflammatory activities position LDPs as good candidates for nutraceutical development for the prevention and management of medical conditions whose etiology are multifactorial. Full article

(This article belongs to the Special Issue Bioactive Peptides)

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