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Bioactive Peptides: Challenges and Opportunities

A topical collection in Nutrients (ISSN 2072-6643). This collection belongs to the section "Proteins and Amino Acids".

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Editor

Department of Pharmaceutical Sciences, University of Milan, via Mangiagalli 25, 20133 Milano, Italy
Interests: food bioactive peptides and food proteins; cholesterol-lowering; hypoglycemic; hypotensive and antioxidants peptides from food
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

In addition to their nutritional value, food proteins provide numerous health benefits through their impact on specific biochemical pathways. Most of these activities are due to peptides encrypted in the parent protein sequences. In the scientific literature, many food peptides are described as exerting a wide range of activities potentially beneficial to health, e.g., antihypertensive, antioxidant, immunomodulatory, anticancer, antimicrobial, and hypocholesterolemic. The ability of food peptides to mediate many of these functional activities is explained by their very diversified structures. Moreover, some of them also show an intrinsically multifunctional behavior, exerting more than one of the physiological effects mentioned above. However, in order to be active, a peptide masked within a protein sequence needs not only to be released by specific and selective proteases but also to be absorbed at the intestinal level and to enter the circulation to reach the target organs inactive form.

The use of bioactive peptides use offers many advantages, including safety, good efficacy and selectivity, and low costs for the health system. For these reasons, they represent a promising tool for the development of functional foods and/or nutraceuticals aimed at improving health and preventing chronic diseases.

Bioactive peptides represent a rapidly developing field of investigation that is attracting the interest of many researchers. Thus, this Collection of Nutrients, entitled “Bioactive Peptides: Challenges and Opportunities”, welcomes the submission of manuscripts either describing original research or reviewing the scientific literature focusing on this very challenging topic.

Dr. Carmen Lammi
Collection Editor

Manuscript Submission Information

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Keywords

  • bioactive peptides
  • multifunctional peptides
  • absorption study
  • enzymatic hydrolysis
  • mechanistic investigation
  • food proteins

Published Papers (15 papers)

2024

Jump to: 2023, 2022

34 pages, 5228 KiB  
Review
The Potential of the Adzuki Bean (Vigna angularis) and Its Bioactive Compounds in Managing Type 2 Diabetes and Glucose Metabolism: A Narrative Review
by Shu Hang Kwan and Elvira Gonzalez de Mejia
Nutrients 2024, 16(2), 329; https://doi.org/10.3390/nu16020329 - 22 Jan 2024
Viewed by 1337
Abstract
Type 2 diabetes (T2D) is a common noncommunicable disease. In the United States alone, 37 million Americans had diabetes in 2017. The adzuki bean (Vigna angularis), a legume, has been reported to possess antidiabetic benefits. However, the extent and specific mechanisms [...] Read more.
Type 2 diabetes (T2D) is a common noncommunicable disease. In the United States alone, 37 million Americans had diabetes in 2017. The adzuki bean (Vigna angularis), a legume, has been reported to possess antidiabetic benefits. However, the extent and specific mechanisms through which adzuki bean consumption may contribute to T2D prevention and management remain unclear. Therefore, the aim of this narrative review is to analyze current evidence supporting the utilization of adzuki beans in the diet as a strategy for preventing and managing T2D. Animal studies have demonstrated a positive impact of adzuki beans on managing T2D. However, supporting data from humans are limited. Conversely, the potential of adzuki bean consumption in preventing T2D via modulating two T2D risk factors (obesity and dyslipidemia) also lacks conclusive evidence. Animal studies have suggested an inconsistent and even contradictory relationship between adzuki bean consumption and the management of obesity and dyslipidemia, in which both positive and negative relationships are reported. In sum, based on the existing scientific literature, this review found that the effects of adzuki bean consumption on preventing and managing T2D in humans remain undetermined. Consequently, human randomized controlled trials are needed to elucidate the potential benefits of the adzuki bean and its bioactive components in the prevention and management of T2D. Full article
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2023

Jump to: 2024, 2022

18 pages, 9225 KiB  
Article
Phycobiliprotein Peptide Extracts from Arthrospira platensis Ameliorate Nonalcoholic Fatty Liver Disease by Modulating Hepatic Lipid Profile and Strengthening Fat Mobilization
by Jing Liu, Huan Wu, Yan Zhang, Changbao Hu, Dongyu Zhen, Pengcheng Fu and Yanfu He
Nutrients 2023, 15(21), 4573; https://doi.org/10.3390/nu15214573 - 27 Oct 2023
Cited by 1 | Viewed by 996
Abstract
Arthrospira platensis phycobiliprotein peptide extracts (PPEs) exhibit potential mitigative effects on hepatic steatosis. However, the precise role of PPEs in addressing high-fat-induced nonalcoholic fatty liver disease (NAFLD), as well as the underlying mechanism, remains to be elucidated. In this study, NAFLD was induced [...] Read more.
Arthrospira platensis phycobiliprotein peptide extracts (PPEs) exhibit potential mitigative effects on hepatic steatosis. However, the precise role of PPEs in addressing high-fat-induced nonalcoholic fatty liver disease (NAFLD), as well as the underlying mechanism, remains to be elucidated. In this study, NAFLD was induced in rats through a high-fat diet (HFD), and the rats were subsequently treated with PPEs for a duration of 10 weeks. The outcomes of this investigation demonstrate that PPE supplementation leads to a reduction in body weight gain, a decrease in the accumulation of lipid droplets within the liver tissues, alterations in hepatic lipid profile, regulation of lipolysis-related gene expression within white adipose tissues and modulation of intestinal metabolites. Notably, PPE supplementation exhibits a potential to alleviate liver damage by manipulating neutral lipid metabolism and phospholipid metabolism. Additionally, PPEs appear to enhance fat mobilization by up-regulating the gene expression levels of key factors such as HSL, TGL, UCP1 and UCP2. Furthermore, PPEs impact intestinal metabolites by reducing the levels of long-chain fatty acids while concurrently increasing the levels of short-chain fatty acids. The findings from this study unveil the potential of PPE intervention in ameliorating NAFLD through the modulation of hepatic lipid profile and the reinforcement of the fat mobilization of intestinal metabolites. Thus, PPEs exhibit noteworthy therapeutic effects in the context of NAFLD. Full article
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14 pages, 3438 KiB  
Article
Whey Protein Hydrolysate Ameliorated High-Fat-Diet Induced Bone Loss via Suppressing Oxidative Stress and Regulating GSK-3β/Nrf2 Signaling Pathway
by Tingting Bu, Ju Huang, Yue Yu, Peilong Sun and Kai Yang
Nutrients 2023, 15(13), 2863; https://doi.org/10.3390/nu15132863 - 24 Jun 2023
Cited by 1 | Viewed by 1311
Abstract
Long-term hypercaloric intake such as a high-fat diet (HFD) could act as negative regulators on bone remodeling, thereby inducing bone loss and bone microarchitecture destruction. Currently, food-derived natural compounds represent a promising strategy to attenuate HFD-induced bone loss. We previously prepared a whey [...] Read more.
Long-term hypercaloric intake such as a high-fat diet (HFD) could act as negative regulators on bone remodeling, thereby inducing bone loss and bone microarchitecture destruction. Currently, food-derived natural compounds represent a promising strategy to attenuate HFD-induced bone loss. We previously prepared a whey protein hydrolysate (WPH) with osteogenic capacity. In this study, we continuously isolated and identified an osteogenic and antioxidant octapeptide TPEVDDA from WPH, which significantly promoted the alkaline phosphatase activities on MC3T3-E1 cells and exerted DPPH radical scavenging capacity. We then established an HFD-fed obese mice model with significantly imbalanced redox status and reduced bone mass and further evaluated the effects of different doses of WPH on ameliorating the HFD-induced bone loss and oxidative damages. Results showed that the administration of 2% and 4% WPH for 12 weeks significantly restored perirenal fat mass, improved serum lipid levels, reduced oxidative stress, and promoted the activity of antioxidant enzymes; meanwhile, WPH significantly preserved bone mass and bone mechanical properties, attenuated the degradation of trabecular microstructure, and regulated serum bone metabolism biomarkers. The protein levels of Runx2, Nrf2, and HO-1, as well as the phosphorylation level of GSK-3β in tibias, were notably activated by WPH. Overall, we found that the potential mechanism of WPH on ameliorating the HFD-induced bone loss mainly through its antioxidant and osteogenic capacity by activating Runx2 and GSK-3β/Nrf2 signaling pathway, demonstrating the potential of WPH to be used as a nutritional strategy for obesity and osteoporosis. Full article
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15 pages, 2101 KiB  
Article
Rainbow Trout (Oncorhynchus mykiss) as Source of Multifunctional Peptides with Antioxidant, ACE and DPP-IV Inhibitory Activities
by Martina Bartolomei, Janna Cropotova, Carlotta Bollati, Kristine Kvangarsnes, Lorenza d’Adduzio, Jianqiang Li, Giovanna Boschin and Carmen Lammi
Nutrients 2023, 15(4), 829; https://doi.org/10.3390/nu15040829 - 06 Feb 2023
Cited by 4 | Viewed by 2317
Abstract
The present study aimed at characterizing the possible biological activities of the multifunctional low molecular weight fractions (<3 kDa) peptides isolated from rainbow trout (Oncorhynchus mykiss) obtained by enzymatic hydrolysis. The fish protein hydrolysate (FPH) was tested for its antioxidant property [...] Read more.
The present study aimed at characterizing the possible biological activities of the multifunctional low molecular weight fractions (<3 kDa) peptides isolated from rainbow trout (Oncorhynchus mykiss) obtained by enzymatic hydrolysis. The fish protein hydrolysate (FPH) was tested for its antioxidant property along with its angiotensin converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibitory activities. In particular, the 2,2-diphenyl-1-picrylhydrazyl (DPPH), the ferric reducing antioxidant power (FRAP), the oxygen radical absorbance capacity (ORAC) assay and the 2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays were carried out for the evaluation of the in vitro antioxidant activity. The cell-free ACE and DPP-IV inhibitory activity assays were also estimated, showing a dose-dependent inhibition. These biological properties were additionally quantified at the cellular level using human intestinal Caco-2 cells. Namely, the antioxidant activity was determined by evaluating the capability of the hydrolysate to reduce the H2O2-induced reactive oxygen species (ROS) and lipid peroxidation levels, and the DPP-IV activity assays show a reduction of enzyme activity of up to 27.57 ± 3.7% at 5 mg/mL. The results indicate that Oncorhynchus mykiss-derived peptides may have potential employment as health-promoting ingredients. Full article
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2022

Jump to: 2024, 2023

15 pages, 3097 KiB  
Article
Purification of Extracellular Protease from Staphylococcus simulans QB7and Its Ability in Generating Antioxidant and Anti-inflammatory Peptides from Meat Proteins
by Hongying Li, Hongbing Fan, Kuan Lu, Qiujin Zhu and Jianping Wu
Nutrients 2023, 15(1), 65; https://doi.org/10.3390/nu15010065 - 23 Dec 2022
Cited by 1 | Viewed by 2205
Abstract
Proteases, especially microbial proteases, are widely used in food processing. The purpose of this study was aimed to purify an extracellular protease produced by the strain Staphylococcus simulans QB7 and to evaluate its ability in hydrolyzing meat proteins and generating antioxidant and anti-inflammatory [...] Read more.
Proteases, especially microbial proteases, are widely used in food processing. The purpose of this study was aimed to purify an extracellular protease produced by the strain Staphylococcus simulans QB7 and to evaluate its ability in hydrolyzing meat proteins and generating antioxidant and anti-inflammatory peptides. The optimal conditions for producing the enzyme were as follows: inoculum ratio, 10%; initial pH, 6.5; temperature, 32 °C; incubation time, 36 h; and rotation speed, 160 rpm. The protease had a molecular weight of approximately 47 kDa, possessing the optimal activity at 50 °C, pH 7.0, The protease was stable at pH 4.0–8.0 and 30–60 °C, and the activity was improved by Na+, Mg2+, Ca2+, and Zn2+ ions, whereas it was inhibited by Cu2+, Co2+, Fe3+, Ba2+, Fe2+, β-M, and ethylene diamine tetraacetic acid disodium salt (EDTA). The protease could effectively hydrolyze meat proteins, and the generated hydrolysate could significantly inhibit tumor necrosis factor-alpha (TNFα)-induced oxidative stress, including superoxide and malondialdehyde levels and inflammation (vascular adhesion molecule-1 [VCAM-1] and cyclooxygenase 2 [COX2)) in human vascular EA.hy926 cells. The present findings support the ability of S. simulans QB7 protease in generating antioxidant and anti-inflammatory peptides during the fermentation of meat products. Full article
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14 pages, 2129 KiB  
Article
Walnut Oligopeptide Delayed Improved Aging-Related Learning and Memory Impairment in SAMP8 Mice
by Qian Du, Meihong Xu, Lan Wu, Rui Fan, Yuntao Hao, Xinran Liu, Ruixue Mao, Rui Liu and Yong Li
Nutrients 2022, 14(23), 5059; https://doi.org/10.3390/nu14235059 - 28 Nov 2022
Cited by 3 | Viewed by 2042
Abstract
Aging-related learning and memory decline are hallmarks of aging and pose a significant health burden. The effects of walnut oligopeptides (WOPs) on learning and memory were evaluated in this study. Sixty SAMP8 mice were randomly divided into four groups (15 mice/group), including one [...] Read more.
Aging-related learning and memory decline are hallmarks of aging and pose a significant health burden. The effects of walnut oligopeptides (WOPs) on learning and memory were evaluated in this study. Sixty SAMP8 mice were randomly divided into four groups (15 mice/group), including one SAMP8 age-control group and three WOP-treated groups. SAMR1 mice (n = 15) that show a normal senescence rate were used as controls. The SAMP8 and SAMR1 controls were administered ordinary sterilized water, while the WOP-intervention groups were administered 110, 220, and 440 mg/kg·bw of WOPs in water, respectively. The whole intervention period was six months. The remaining 15 SAMP8 (4-month-old) mice were used as the young control group. The results showed that WOPs significantly improved the decline in aging-related learning/memory ability. WOPs significantly increased the expression of BDNF and PSD95 and decreased the level of APP and Aβ1-42 in the brain. The mechanism of action may be related to an increase in the activity of antioxidant enzymes (SOD and GSH-Px), a reduction in the expression of inflammatory factors (TNF-α and IL-1β) in the brain and a reduction in oxidative stress injury (MDA). Furthermore, the expression of AMPK, SIRT-1, and PGC-1α was upregulated and the mitochondrial DNA content was increased in brain. These results indicated that WOPs improved aging-related learning and memory impairment. WOP supplementation may be a potential and effective method for the elderly. Full article
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13 pages, 1819 KiB  
Article
An In Silico Framework to Mine Bioactive Peptides from Annotated Proteomes: A Case Study on Pancreatic Alpha Amylase Inhibitory Peptides from Algae and Cyanobacteria
by Lorenzo Pedroni, Florinda Perugino, Gianni Galaverna, Chiara Dall’Asta and Luca Dellafiora
Nutrients 2022, 14(21), 4680; https://doi.org/10.3390/nu14214680 - 04 Nov 2022
Cited by 1 | Viewed by 1701
Abstract
Bioactive peptides may exert beneficial activities in living organisms such as the regulation of glucose metabolism through the inhibition of alpha amylases. Algae and cyanobacteria are gaining a growing interest for their health-promoting properties, and possible effects on glucose metabolism have been described, [...] Read more.
Bioactive peptides may exert beneficial activities in living organisms such as the regulation of glucose metabolism through the inhibition of alpha amylases. Algae and cyanobacteria are gaining a growing interest for their health-promoting properties, and possible effects on glucose metabolism have been described, although the underlying mechanisms need clarification. This study proposes a computer-driven workflow for a proteome-wide mining of alpha amylase inhibitory peptides from the proteome of Chlorella vulgaris, Auxenochlorella protothecoides and Aphanizomenon flos-aquae. Overall, this work presents an innovative and versatile approach to support the identification of bioactive peptides in annotated proteomes. The study: (i) highlighted the presence of alpha amylase inhibitory peptides within the proteomes under investigation (including ELS, which is among the most potent inhibitory tripeptides identified so far); (ii) mechanistically investigated the possible mechanisms of action; and (iii) prioritized further dedicated investigation on the proteome of C. vulgaris and A. flos-aquae, and on CSSL and PGG sequences. Full article
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19 pages, 2169 KiB  
Review
Critical Review for the Production of Antidiabetic Peptides by a Bibliometric Approach
by Ticiane Carvalho Farias, Thaiza Serrano Pinheiro de Souza, Ana Elizabeth Cavalcante Fai and Maria Gabriela Bello Koblitz
Nutrients 2022, 14(20), 4275; https://doi.org/10.3390/nu14204275 - 14 Oct 2022
Cited by 2 | Viewed by 2058
Abstract
The current bibliometric review evaluated recent papers that researched dietary protein sources to generate antidiabetic bioactive peptides/hydrolysates for the management of diabetes. Scopus and PubMed databases were searched to extract bibliometric data and, after a systematic four-step process was performed to select the [...] Read more.
The current bibliometric review evaluated recent papers that researched dietary protein sources to generate antidiabetic bioactive peptides/hydrolysates for the management of diabetes. Scopus and PubMed databases were searched to extract bibliometric data and, after a systematic four-step process was performed to select the articles, 75 papers were included in this review. The countries of origin of the authors who published the most were China (67%); Ireland (59%); and Spain (37%). The journals that published most articles on the subject were Food Chemistry (n = 12); Food & Function (n = 8); and Food Research International (n = 6). The most used keywords were ‘bioactive peptides’ (occurrence 28) and ‘antidiabetic’ (occurrence 10). The most used enzymes were Alcalase® (17%), Trypsin (17%), Pepsin, and Flavourzyme® (15% each). It was found that different sources of protein have been used to generate dipeptidyl peptidase IV (DPP-IV), α-amylase, and α-glucosidase inhibitory peptides. In addition to antidiabetic properties, some articles (n = 30) carried out studies on multifunctional bioactive peptides, and the most cited were reported to have antioxidant and antihypertensive activities (n = 19 and 17, respectively). The present review intended to offer bibliometric data on the most recent research on the production of antidiabetic peptides from dietary proteins to those interested in their obtention to act as hypoglycemic functional ingredients. The studies available in this period, compiled, are not yet enough to point out the best strategies for the production of antidiabetic peptides from food proteins and a more systematic effort in this direction is necessary to allow a future scale-up for the production of these possible functional ingredients. Full article
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13 pages, 43217 KiB  
Article
Alanyl-Glutamine Protects Mice against Methionine- and Choline-Deficient-Diet-Induced Steatohepatitis and Fibrosis by Modulating Oxidative Stress and Inflammation
by Jiaji Hu, Yigang Zheng, Hanglu Ying, Huabin Ma, Long Li and Yufen Zhao
Nutrients 2022, 14(18), 3796; https://doi.org/10.3390/nu14183796 - 15 Sep 2022
Cited by 1 | Viewed by 2655
Abstract
Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease with increasing prevalence rates over years and is associated with hepatic lipid accumulation, liver injury, oxidative stress, hepatic inflammation, and liver fibrosis and lack of approved pharmacological therapy. Alanyl-glutamine (Ala-Gln) is a recognized gut-trophic [...] Read more.
Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease with increasing prevalence rates over years and is associated with hepatic lipid accumulation, liver injury, oxidative stress, hepatic inflammation, and liver fibrosis and lack of approved pharmacological therapy. Alanyl-glutamine (Ala-Gln) is a recognized gut-trophic nutrient that has multiple pharmacological effects in the prevention of inflammation- and oxidative-stress-associated diseases. Nevertheless, whether Ala-Gln has a protective effect on NASH still lacks evidence. The aim of this study is to explore the influence of Ala-Gln on NASH and its underlying mechanisms. Here, C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet to establish the model of NASH, and Ala-Gln at doses of 500 and 1500 mg/kg were intraperitoneally administered to mice along with a MCD diet. The results showed that Ala-Gln treatment significantly attenuated MCD-induced hepatic pathological changes, lowered NAFLD activity score, and reduced plasma alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) levels. Ala-Gln dramatically alleviated lipid accumulation in liver through modulating the expression levels of fatty acid translocase (FAT/CD36) and farnesoid X receptor (FXR). In addition, Ala-Gln exerted an anti-oxidant effect by elevating the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, Ala-Gln exhibited an anti-inflammatory effect via decreasing the accumulation of activated macrophages and suppressing the production of proinflammatory mediators. Notably, Ala-Gln suppressed the development of liver fibrosis in MCD-diet-fed mice, which may be due to the inhibition of hepatic stellate cells activation. In conclusion, these findings revealed that Ala-Gln prevents the progression of NASH through the modulation of oxidative stress and inflammation and provided the proof that Ala-Gln might be an effective pharmacological agent to treat NASH. Full article
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16 pages, 3065 KiB  
Article
A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells
by Tingting Bu, Yuting Ren, Songfeng Yu, Jiexia Zheng, Ling Liu, Peilong Sun, Jianping Wu and Kai Yang
Nutrients 2022, 14(15), 3135; https://doi.org/10.3390/nu14153135 - 29 Jul 2022
Cited by 2 | Viewed by 1652
Abstract
A phenylalanine (Phe)-restricted diet is indispensable for individuals suffering from phenylketonuria (PKU). Our previous study reported a low-Phe-containing whey protein hydrolysate (LPH) prepared from a selected whey protein hydrolysate (TA2H). This study aimed to investigate the osteogenic activity of LPH and TA2H in [...] Read more.
A phenylalanine (Phe)-restricted diet is indispensable for individuals suffering from phenylketonuria (PKU). Our previous study reported a low-Phe-containing whey protein hydrolysate (LPH) prepared from a selected whey protein hydrolysate (TA2H). This study aimed to investigate the osteogenic activity of LPH and TA2H in MC3T3-E1 preosteoblast cells and explore the underlying mechanism. Results showed that the treatment of TA2H and LPH (at the final concentrations of 100–1000 μg/mL) had a stimulatory effect on the proliferation, differentiation, and mineralization of MC3T3-E1 cells. The LPH of 1000 μg/mL significantly increased cell proliferation (2.15- ± 0.11-fold) and alkaline phosphatase activity (1.22- ± 0.07-fold), promoted the protein and mRNA levels of runt-related transcription factor 2 (Runx2, 2.50- ± 0.14-fold and 2.97- ± 0.23-fold, respectively), enhanced the expression of differentiation biomarkers (type-I collagen, osteocalcin, and osteopontin), increased calcium deposition (1.56- ± 0.08-fold), and upregulated the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand. The exploration of signaling pathways indicated that the activated p38-dependent Runx2 signaling contributed to the LPH-induced osteogenesis. These results provided evidence, for the first time, that a prepared low-Phe whey protein hydrolysate positively modulated the activity of osteoblasts through the p38/Runx2 pathway, thereby providing a new osteoinductive protein substitute to make functional PKU food. Full article
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23 pages, 917 KiB  
Review
Health-Promoting and Therapeutic Attributes of Milk-Derived Bioactive Peptides
by Mrinal Samtiya, Sweta Samtiya, Prarabdh C. Badgujar, Anil Kumar Puniya, Tejpal Dhewa and Rotimi E. Aluko
Nutrients 2022, 14(15), 3001; https://doi.org/10.3390/nu14153001 - 22 Jul 2022
Cited by 24 | Viewed by 3583
Abstract
Milk-derived bioactive peptides (BAPs) possess several potential attributes in terms of therapeutic capacity and their nutritional value. BAPs from milk proteins can be liberated by bacterial fermentation, in vitro enzymatic hydrolysis, food processing, and gastrointestinal digestion. Previous evidence suggested that milk protein-derived BAPs [...] Read more.
Milk-derived bioactive peptides (BAPs) possess several potential attributes in terms of therapeutic capacity and their nutritional value. BAPs from milk proteins can be liberated by bacterial fermentation, in vitro enzymatic hydrolysis, food processing, and gastrointestinal digestion. Previous evidence suggested that milk protein-derived BAPs have numerous health-beneficial characteristics, including anti-cancerous activity, anti-microbial activity, anti-oxidative, anti-hypertensive, lipid-lowering, anti-diabetic, and anti-osteogenic. In this literature overview, we briefly discussed the production of milk protein-derived BAPs and their mechanisms of action. Milk protein-derived BAPs are gaining much interest worldwide due to their immense potential as health-promoting agents. These BAPs are now used to formulate products sold in the market, which reflects their safety as natural compounds. However, enhanced commercialization of milk protein-derived BAPs depends on knowledge of their particular functions/attributes and safety confirmation using human intervention trials. We have summarized the therapeutic potentials of these BAPs based on data from in vivo and in vitro studies. Full article
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12 pages, 1135 KiB  
Article
Oxidative Stress Protection by Canary Seed (Phalaris canariensis L.) Peptides in Caco-2 Cells and Caenorhabditis elegans
by Uriel Urbizo-Reyes, Kee-Hong Kim, Lavanya Reddivari, Joseph M. Anderson and Andrea M. Liceaga
Nutrients 2022, 14(12), 2415; https://doi.org/10.3390/nu14122415 - 10 Jun 2022
Cited by 2 | Viewed by 2008
Abstract
During oxidative stress, degenerative diseases such as atherosclerosis, Alzheimer’s, and certain cancers are likely to develop. Recent research on canary seed (Phalaris canariensis) peptides has demonstrated the high in vitro antioxidant potential. Thus, this study aimed to assess the cellular and [...] Read more.
During oxidative stress, degenerative diseases such as atherosclerosis, Alzheimer’s, and certain cancers are likely to develop. Recent research on canary seed (Phalaris canariensis) peptides has demonstrated the high in vitro antioxidant potential. Thus, this study aimed to assess the cellular and in vivo antioxidant capacity of a low-molecular-weight (<3 kDa) canary seed peptide fraction (CSPF) using Caco-2 cells and the Caenorhabditis elegans model. The results show that the CSPF had no cytotoxicity effect on Caco-2 cells at any tested concentration (0.3–2.5 mg/mL). Additionally, the cellular antioxidant activity (CAA) of the CSPF was concentration-dependent, and the highest activity achieved was 80% by the CSPF at 2.5 mg/mL. Similarly, incubation with the CSPF significantly mitigated the acute and chronic oxidative damage, extending the lifespan of the nematodes by 88 and 61%, respectively. Furthermore, it was demonstrated that the CSPF reduced the accumulation of reactive oxygen species (ROS) to safe levels after sub-lethal doses of pro-oxidant paraquat. Quantitative real-time PCR revealed that the CSPF increased the expression of oxidative-stress-response-related gene GST-4. Overall, these results show that the CSPFs relied on GST-4 upregulation and scavenging of free radicals to confer oxidative stress protection and suggest that a CSPF can be used as a natural antioxidant in foods for health applications. Full article
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14 pages, 2210 KiB  
Article
Integrated Evaluation of the Multifunctional DPP-IV and ACE Inhibitory Effect of Soybean and Pea Protein Hydrolysates
by Carlotta Bollati, Ruoxian Xu, Giovanna Boschin, Martina Bartolomei, Fabrizio Rivardo, Jianqiang Li, Anna Arnoldi and Carmen Lammi
Nutrients 2022, 14(12), 2379; https://doi.org/10.3390/nu14122379 - 08 Jun 2022
Cited by 7 | Viewed by 2331
Abstract
Nowadays, notwithstanding their nutritional and technological properties, food bioactive peptides from plant sources garner increasing attention for their ability to impart more than one beneficial effect on human health. Legumes, which stand out thanks to their high protein content, represent valuable sources of [...] Read more.
Nowadays, notwithstanding their nutritional and technological properties, food bioactive peptides from plant sources garner increasing attention for their ability to impart more than one beneficial effect on human health. Legumes, which stand out thanks to their high protein content, represent valuable sources of bioactive peptides. In this context, this study focused on the characterization of the potential pleotropic activity of two commercially available soybean (SH) and pea (PH) protein hydrolysates, respectively. Since the biological activity of a specific protein hydrolysate is strictly correlated with its chemical composition, the first aim of the study was to identify the compositions of the SH and PH peptides. Peptidomic analysis revealed that most of the identified peptides within both mixtures belong to storage proteins. Interestingly, according to the BIOPEP-UWM database, all the peptides contain more than one active motive with known inhibitory angiotensin converting enzyme (ACE) and dipeptidyl-dipeptidases (DPP)-IV sequences. Indeed, the results indicated that both SH and PH inhibit DPP-IV and ACE activity with a dose-response trend and IC50 values equal to 1.15 ± 0.004 and 1.33 ± 0.004 mg/mL, and 0.33 ± 0.01 and 0.61 ± 0.05 mg/mL, respectively. In addition, both hydrolysates reduced the activity of DPP-IV and ACE enzymes which are expressed on the surface of human intestinal Caco-2 cells. These findings clearly support that notion that SH and PH may represent new ingredients with anti-diabetic and hypotensive effects for the development of innovative multifunctional foods and/or nutraceuticals for the prevention of metabolic syndrome. Full article
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13 pages, 1944 KiB  
Article
Hempseed (Cannabis sativa) Peptide H3 (IGFLIIWV) Exerts Cholesterol-Lowering Effects in Human Hepatic Cell Line
by Jianqiang Li, Carlotta Bollati, Martina Bartolomei, Angelica Mazzolari, Anna Arnoldi, Giulio Vistoli and Carmen Lammi
Nutrients 2022, 14(9), 1804; https://doi.org/10.3390/nu14091804 - 26 Apr 2022
Cited by 11 | Viewed by 2372
Abstract
Hempseed (Cannabis sativa) protein is an important source of bioactive peptides. H3 (IGFLIIWV), a transepithelial transported intestinal peptide obtained from the hydrolysis of hempseed protein with pepsin, carries out antioxidant and anti-inflammatory activities in HepG2 cells. In this study, the main [...] Read more.
Hempseed (Cannabis sativa) protein is an important source of bioactive peptides. H3 (IGFLIIWV), a transepithelial transported intestinal peptide obtained from the hydrolysis of hempseed protein with pepsin, carries out antioxidant and anti-inflammatory activities in HepG2 cells. In this study, the main aim was to assess its hypocholesterolemic effects at a cellular level and the mechanisms behind this health-promoting activity. The results showed that peptide H3 inhibited the 3-hydroxy-3-methylglutaryl co-enzyme A reductase (HMGCoAR) activity in vitro in a dose-dependent manner with an IC50 value of 59 μM. Furthermore, the activation of the sterol regulatory element binding proteins (SREBP)-2 transcription factor, followed by the increase of low-density lipoprotein (LDL) receptor (LDLR) protein levels, was observed in human hepatic HepG2 cells treated with peptide H3 at 25 µM. Meanwhile, peptide H3 regulated the intracellular HMGCoAR activity through the increase of its phosphorylation by the activation of AMP-activated protein kinase (AMPK)-pathways. Consequently, the augmentation of the LDLR localized on the cellular membranes led to the improved ability of HepG2 cells to uptake extracellular LDL with a positive effect on cholesterol levels. Unlike the complete hempseed hydrolysate (HP), peptide H3 can reduce the proprotein convertase subtilisin/kexin 9 (PCSK9) protein levels and its secretion in the extracellular environment via the decrease of hepatic nuclear factor 1-α (HNF1-α). Considering all these evidences, H3 may represent a new bioactive peptide to be used for the development of dietary supplements and/or peptidomimetics for cardiovascular disease (CVD) prevention. Full article
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12 pages, 1826 KiB  
Article
Cyclo(His-Pro) Exerts Protective Carbonyl Quenching Effects through Its Open Histidine Containing Dipeptides
by Luca Regazzoni, Laura Fumagalli, Angelica Artasensi, Silvia Gervasoni, Ettore Gilardoni, Angelica Mazzolari, Giancarlo Aldini and Giulio Vistoli
Nutrients 2022, 14(9), 1775; https://doi.org/10.3390/nu14091775 - 23 Apr 2022
Cited by 4 | Viewed by 2101
Abstract
Cyclo(His-Pro) (CHP) is a cyclic dipeptide which is endowed with favorable pharmacokinetic properties combined with a variety of biological activities. CHP is found in a number of protein-rich foods and dietary supplements. While being stable at physiological pH, CHP can open yielding two [...] Read more.
Cyclo(His-Pro) (CHP) is a cyclic dipeptide which is endowed with favorable pharmacokinetic properties combined with a variety of biological activities. CHP is found in a number of protein-rich foods and dietary supplements. While being stable at physiological pH, CHP can open yielding two symmetric dipeptides (His-Pro, Pro-His), the formation of which might be particularly relevant from dietary CHP due to the gastric acidic environment. The antioxidant and protective CHP properties were repeatedly reported although the non-enzymatic mechanisms were scantly investigated. The CHP detoxifying activity towards α,β unsaturated carbonyls was never investigated in detail, although its open dipeptides might be effective as already observed for histidine containing dipeptides. Hence, this study investigated the scavenging properties of TRH, CHP and its open derivatives towards 4-hydroxy-2-nonenal. The obtained results revealed that Pro-His possesses a marked activity and is more reactive than l-carnosine. As investigated by DFT calculations, the enhanced reactivity can be ascribed to the greater electrophilicity of the involved iminium intermediate. These findings emphasize that the primary amine (as seen in l-carnosine) can be replaced by secondary amines with beneficial effects on the quenching mechanisms. Serum stability of the tested peptides was also evaluated, showing that Pro-His is characterized by a greater stability than l-carnosine. Docking simulations suggested that its hydrolysis can be catalyzed by serum carnosinase. Altogether, the reported results evidence that the antioxidant CHP properties can be also due to the detoxifying activity of its open dipeptides, which might be thus responsible for the beneficial effects induced by CHP containing food. Full article
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