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Bioactive Peptides in Health and Disease
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Bioactive Peptides in Health and Disease

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 14726

Special Issue Editors

Dr. Luigia Pazzagli

E-Mail Website
Guest Editor
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Firenze, Italy
Interests: proteins and peptides; amino acids; enzymology; protein purification techniques; protein characterization; anti-oxidant and anti-inflammatory molecules; plant defences
Special Issues, Collections and Topics in MDPI journals
Dr. Simone Luti

E-Mail Website
Guest Editor
Department of Biomedical Sciences Experimental and Clinical, University of Florence, 50121 Firenze, Italy
Interests: protein and peptide structural and functional characterization; nutraceuticals from plant sources; oxidative stress in plant and human tissues

Special Issue Information

Dear Colleagues,

The proverbial saying 'You are what you eat' from the German philosopher Feuerbach is becoming increasingly more in agreement with recent findings concerning nutraceutical foods, with a plethora of studies having been conducted studying the role of food-derived phytochemicals. While polyphenolic compounds have attracted attention for several years, in recent times, short protein fragments exhibiting biological activities have received significant interest. Consequently, bioactive peptides from both plant and animal proteins have been discovered, and applications in the formulation of functional foods, nutraceuticals, and therapeutic agents have increasingly gained scholarly and industrial attention.

In this Special Issue, we invite submissions exploring bioactive food proteins, with particular emphasis on bioactive hydrolysates and peptides derived from food proteins. Recent evidence suggests that bioactive peptides can have different biological roles on human health, including antimicrobial, antiproliferative, antioxidant, blood-pressure-lowering, and antithrombotic, but difficulties in the setting up of production methods, as well as in determining their digestion and adsorption rate, have delayed their commercial use. Possible topics range from the structural and functional characterization of bioactive peptides to the determination of their biological properties on human health and disease. Considerations regarding the stability, bioavailability, and techno-functional properties of such components, as well as the design and characterization of plant and animal functional foods are also welcome.

We are pleased to invite you to submit your work to the Special Issue entitled ‘Bioactive Peptides in Health and Disease’, within the Biology journal. Bioactive peptides are considered to be a novel generation of biologically active regulators that not only prevent the mechanism of oxidation and microbial degradation in foods, but also enhance the treatment of various diseases and disorders, thus, increasing quality of life.

This Special Issue aims to deepen the currently available knowledge on bioactive peptides in foods and other sources. Naturally fermented as well as hydrolyzed foods are good sources of bioactive peptides; the characterization of their production methods, biological activity and role in wellness and in the prevention and/or treatment of pathological conditions are topics worthy of consideration.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: the production of bioactive peptides from food, marine, as well as plant and animal sources; the production of peptides using hydrolysis, fermentation, and in vitro synthesis; the characterization of their biological activity with in vitro and in vivo experiments. The determination of the stability, bioavailability, and techno-functional properties of peptides and in silico design and characterization are also welcome.

We look forward to receiving your contributions.

Prof. Dr. Luigia Pazzagli
Dr. Simone Luti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • amino acid sequences
  • bacterial proteases
  • bioactive peptides
  • chemical and enzymatic hydrolysis
  • nutraceutical foods
  • healthy activity
  • plant and animal sources

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Published Papers (7 papers)

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Research

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15 pages, 2440 KiB  
Article
Identification of a Novel Bioactive Peptide Derived from Frozen Chicken Breast Hydrolysate and the Utilization of Hydrolysates as Biopreservatives
by Mohamed Abdelfattah Maky and Takeshi Zendo
Biology 2023, 12(9), 1218; https://doi.org/10.3390/biology12091218 - 8 Sep 2023
Cited by 1 | Viewed by 1596
Abstract
Frozen chicken breast was hydrolyzed by treatment with thermolysin enzyme to obtain a chicken hydrolysate containing bioactive peptides. After that, a peptide was purified from the chicken hydrolysate utilizing a Sep-Pak C18 cartridge and reversed-phase high-performance liquid chromatography (RP-HPLC). The molecular weight of [...] Read more.
Frozen chicken breast was hydrolyzed by treatment with thermolysin enzyme to obtain a chicken hydrolysate containing bioactive peptides. After that, a peptide was purified from the chicken hydrolysate utilizing a Sep-Pak C18 cartridge and reversed-phase high-performance liquid chromatography (RP-HPLC). The molecular weight of the chicken peptide was 2766.8. Protein sequence analysis showed that the peptide was composed of 25 amino acid residues. The peptide, designated as C25, demonstrated an inhibitory action on the angiotensin-converting enzyme (ACE) with a half maximal inhibitory concentration (IC50) value of 1.11 µg/mL. Interestingly, C25 showed antimicrobial activity against multi-drug resistant bacteria Proteus vulgaris F24B and Escherichia coli JM109, both with MIC values of 24 µg/mL. The chicken hydrolysate showed antioxidant activity with an IC50 value of 348.67 µg/mL. Furthermore, the proliferation of aerobic bacteria and Enterobacteriaceae as well as lipid oxidation were significantly reduced when the chicken hydrolysate was used as a natural preservative during cold storage of chicken breasts. Hydrolysates derived from muscle sources have the potential to be used in formulated food products and to contribute positively to human health. Full article
(This article belongs to the Special Issue Bioactive Peptides in Health and Disease)
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15 pages, 2506 KiB  
Article
Effect of Bovine Milk Peptides on Cell Inflammation, Proliferation and Differentiation: Milk Potential Benefits Are Preserved in an Unconventional Cow Feeding Strategy
by Costanza Cicchi, Paolo Paoli, Alessandra Modesti, Federica Mannelli, Federica Scicutella, Arianna Buccioni, Carolina Fontanarosa, Simone Luti and Luigia Pazzagli
Biology 2023, 12(9), 1162; https://doi.org/10.3390/biology12091162 - 23 Aug 2023
Viewed by 1680
Abstract
Animal feeding through the reuse of agro-industrial by-products in one of the ultimate goals of sustainable agriculture. Olive oil pomace (OOP) produced as a waste product during olive oil milling has been used as an ingredient in the diet for Holstein lactating cows. [...] Read more.
Animal feeding through the reuse of agro-industrial by-products in one of the ultimate goals of sustainable agriculture. Olive oil pomace (OOP) produced as a waste product during olive oil milling has been used as an ingredient in the diet for Holstein lactating cows. Recent findings have shown no decrease in animal performance, feed intake or detrimental effect on rumen microbiota. In contrast, an improvement in C18 polyunsaturated fatty acids has been observed. In this work, the milk protein content from cows fed a commercial diet (CON) or an experimental one supplemented with OOP was determined and compared, and the peptides derived from the simulated gastrointestinal digestion of raw milk were analyzed. After fractionation via RP-HPLC, peptides were characterized for their biological activity on different cell lines. The ability to reduce both the intracellular ROS content and the expression of inflammatory markers, such as Cyclooxygenase, isoenzyme 2 (COX-2) and inducible Nitric Oxide Synthase (iNOS), as well as the remarkable properties to induce cell differentiation and to slow down the proliferation of human intestinal cancer cells, enable us to define them as bioactive peptides. In spite of there being no observed significant difference between the healthy activity of CON and OOP peptides, the results allow us to broaden the knowledge about the biological activity of these bioactive peptides and to confirm that agro-industrial by-products may be successfully incorporated into the feeding strategy of dairy cows. Full article
(This article belongs to the Special Issue Bioactive Peptides in Health and Disease)
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23 pages, 6848 KiB  
Article
Effect of Ripening and In Vitro Digestion on Bioactive Peptides Profile in Ras Cheese and Their Biological Activities
by Ahmed Helal, Alice Cattivelli, Angela Conte and Davide Tagliazucchi
Biology 2023, 12(7), 948; https://doi.org/10.3390/biology12070948 - 2 Jul 2023
Cited by 4 | Viewed by 1800
Abstract
The effect of ripening and in vitro digestion on the biological activities, peptide profiles and release of bioactive peptides in Ras cheese has been investigated. Ras cheese ripening largely influenced the extent of protein hydrolysis. The advancement in ripening resulted in an increase [...] Read more.
The effect of ripening and in vitro digestion on the biological activities, peptide profiles and release of bioactive peptides in Ras cheese has been investigated. Ras cheese ripening largely influenced the extent of protein hydrolysis. The advancement in ripening resulted in an increase in total peptides (from 0.97 to 2.46 mmol leucine/g in samples at 30 and 180 days of ripening, respectively) and bioactive peptides concentration, especially angiotensin-converting enzyme (ACE)-inhibitory, dipeptidyl-peptidase-IV-(DPP-IV)-inhibitory and antioxidant peptides. In vitro gastro-intestinal digestion further promoted protein hydrolysis and the release of bioactive peptides. Digested Ras cheese at 90 and 180 days of ripening displayed the highest bioactive peptides intensity. The variations in bioactive peptides amount during ripening and in vitro digestion were correlated with the changes in ACE-inhibitory, DPP-IV-inhibitory and antioxidant activities. The highest amounts of VPP and IPP were detected in digested Ras cheese at 90 days of ripening (17.44 and 36.50 mg/kg of cheese, respectively), whereas the highest concentrations of APFPE were found in undigested and digested 180-day ripened Ras cheese (82.09 and 52.01 mg/kg of cheese, respectively). The present investigation underlined potential differences in the biological effect after the ingestion of Ras cheese at different ripening times. Full article
(This article belongs to the Special Issue Bioactive Peptides in Health and Disease)
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12 pages, 2291 KiB  
Article
Tripeptide IRW Improves AMPK/eNOS Signaling Pathway via Activating ACE2 in the Aorta of High-Fat-Diet-Fed C57BL/6 Mice
by Fatemeh Ashkar, Khushwant S. Bhullar, Xu Jiang and Jianping Wu
Biology 2023, 12(4), 556; https://doi.org/10.3390/biology12040556 - 6 Apr 2023
Viewed by 2118
Abstract
This study aims to investigate the effect of tripeptide IRW on the local renin–angiotensin system (RAS), particularly angiotensin-converting enzyme 2 (ACE2), and their association with signaling pathways in the aorta of a high-fat-diet (HFD)-induced insulin-resistant mouse model. C57BL/6 mice were fed HFD (45% [...] Read more.
This study aims to investigate the effect of tripeptide IRW on the local renin–angiotensin system (RAS), particularly angiotensin-converting enzyme 2 (ACE2), and their association with signaling pathways in the aorta of a high-fat-diet (HFD)-induced insulin-resistant mouse model. C57BL/6 mice were fed HFD (45% of the total calories) for six weeks, and then IRW was added to the diet (45 mg/kg body weight (BW)) for another eight weeks. ACE2 mRNA expression and protein level(s) were increased (p < 0.05), while angiotensin II receptor (AT1R) and angiotensin-converting enzyme (ACE) protein abundance was significantly reduced (p < 0.05) in the aorta of HFD mice treated by IRW. IRW supplementation also improved glucose transporter 4 (GLUT4) abundance (p < 0.05) alongside AMP-activated protein kinase (AMPK) (p < 0.05), Sirtuin 1 (SIRT1) (p < 0.05), and endothelial nitric oxide synthase (eNOS) (p < 0.05) expression. IRW downregulated the levels of endothelin 1 (ET-1) and p38 mitogen-activated protein kinases (p38 MAPK, p < 0.05). Furthermore, the levels of AMPK and eNOS in vascular smooth muscle cells (VSMCs) were significantly reduced in ACE2 knockdown cells treated with or without IRW (p < 0.01). In conclusion, this study provided new evidence of the regulatory role of IRW on the aortic ACE2 against metabolic syndrome (MetS) in an HFD-induced insulin-resistant model. Full article
(This article belongs to the Special Issue Bioactive Peptides in Health and Disease)
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16 pages, 1386 KiB  
Article
Hemp Protein Hydrolysates Modulate Inflammasome-Related Genes in Microglial Cells
by Sergio Montserrat-de la Paz, Gabriela Carrillo-Berdasco, Fernando Rivero-Pino, Alvaro Villanueva-Lazo and Maria C. Millan-Linares
Biology 2023, 12(1), 49; https://doi.org/10.3390/biology12010049 - 27 Dec 2022
Cited by 6 | Viewed by 2409
Abstract
A prolonged inflammatory response can lead to the development of neurodegenerative diseases such as Alzheimer’s disease. Enzymatic hydrolysis is a sustainable way to increase the value of protein sources by obtaining peptides that can exert bioactivity. Hemp (Cannabis sativa L.) protein hydrolysates [...] Read more.
A prolonged inflammatory response can lead to the development of neurodegenerative diseases such as Alzheimer’s disease. Enzymatic hydrolysis is a sustainable way to increase the value of protein sources by obtaining peptides that can exert bioactivity. Hemp (Cannabis sativa L.) protein hydrolysates have been proven to exert anti-inflammatory activity. In this study, two hemp protein hydrolysate (HPHs), obtained with Alcalase as sole catalyst, or with Alcalase followed by Flavourzyme, were evaluated as inflammatory mediators (TNFα, IL-1β, IL-6, and IL-10), microglial polarization markers (Ccr7, iNos, Arg1, and Ym1), and genes related to inflammasome activation (Nlrp3, Asc, Casp1, and Il18), employing the lipopolysaccharide (LPS)-induced neuroinflammation model in murine BV-2 microglial cells. A significant decrease of the expression of proinflammatory genes (e.g., Tnfα, Ccr7, inos, and Nlrp3, among others) and increase of the expression anti-inflammatory cytokines in microglial cells was observed after treatment with the test HPHs. This result in the cell model suggests a polarization toward an anti-inflammatory M2 phenotype. Our results show that the evaluated HPHs show potential neuroprotective activity in microglial cells via the inflammasome. Full article
(This article belongs to the Special Issue Bioactive Peptides in Health and Disease)
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17 pages, 1035 KiB  
Article
Alleviation of Cognitive and Physical Fatigue with Enzymatic Porcine Placenta Hydrolysate Intake through Reducing Oxidative Stress and Inflammation in Intensely Exercised Rats
by Min Ju Kim, Ting Zhang, Keun Nam Kim, Gun Won Bae, Sun Myung Yoon, Yu Yue, Xuangao Wu and Sunmin Park
Biology 2022, 11(12), 1739; https://doi.org/10.3390/biology11121739 - 29 Nov 2022
Cited by 3 | Viewed by 1904
Abstract
Intense exercise is reported to induce physical and cognitive fatigue, but few studies have focused on treatments to alleviate fatigue. We hypothesized that the oral supplementation of enzymatic porcine placenta hydrolysate (EPPH) prepared using protease enzymes could alleviate exercise-induced fatigue in an animal [...] Read more.
Intense exercise is reported to induce physical and cognitive fatigue, but few studies have focused on treatments to alleviate fatigue. We hypothesized that the oral supplementation of enzymatic porcine placenta hydrolysate (EPPH) prepared using protease enzymes could alleviate exercise-induced fatigue in an animal model. The objectives of the study were to examine the hypothesis and the action mechanism of EPPH in relieving physical and cognitive fatigue. Fifty male Sprague–Dawley rats aged 8 weeks (body weight: 201 g) were classified into five groups, and rats in each group were given oral distilled water, EPPH (5 mg nitrogen/mL) at doses of 0.08, 0.16, or 0.31 mL/kg body weight (BW)/day, or glutathione (100 mg/kg BW/day) by a feeding needle for 5 weeks, which were named as the control, L-EPPH, M-EPPH, H-EPPH, or positive-control groups, respectively. Ten additional rats had no intense exercise with water administration and were designated as the no-exercise group. After 2 weeks, the rats were subjected to intense exercise and forced swimming trial for 30 min once per week for an additional 4 weeks. At 5 min after the intense exercise, lactate concentrations and lactate dehydrogenase (LDH) activity in the serum and the gastrocnemius muscle were higher in the control group, whereas M-EPPH and H-EPPH treatments suppressed the increase better than in the positive-control (p < 0.05). Intense exercise decreased glycogen content in the liver and gastrocnemius muscle, and M-EPPH and H-EPPH inhibited the decrement (p < 0.05). Moreover, lipid peroxide contents in the gastrocnemius muscle and liver were higher in the control group than in the M-EPPH, H-EPPH, positive-control, and no-exercise groups (p < 0.05). However, antioxidant enzyme activities such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were opposite to the lipid peroxide contents. Hypothalamic corticosterone and hippocampal mRNA expressions of tumor necrosis factor (TNF)-α and IL-1β were higher. However, hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression and protein contents were lower in the control group than in the positive-control group. M-EPPH, H-EPPH, and positive-control suppressed the changes via activating hippocampal cAMP response element-binding protein phosphorylation, and H-EPPH showed better activity than in the positive-control (p < 0.05). In conclusion, EPPH (0.16–0.31 mL/kg BW) intake reduced exercise-induced physical and cognitive fatigue in rats and could potentially be developed as a therapeutic agent for relieving fatigue in humans. Full article
(This article belongs to the Special Issue Bioactive Peptides in Health and Disease)
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Review

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16 pages, 2499 KiB  
Review
Bioactive Peptides and Protein Hydrolysates as Lipoxygenase Inhibitors
by Fai-Chu Wong and Tsun-Thai Chai
Biology 2023, 12(7), 917; https://doi.org/10.3390/biology12070917 - 27 Jun 2023
Cited by 5 | Viewed by 2239
Abstract
Lipoxygenases are non-heme iron-containing enzymes that catalyze the oxidation of polyunsaturated fatty acids, resulting in the production of lipid hydroperoxides, which are precursors of inflammatory lipid mediators. These enzymes are widely distributed in humans, other eukaryotes, and cyanobacteria. Lipoxygenases hold promise as therapeutic [...] Read more.
Lipoxygenases are non-heme iron-containing enzymes that catalyze the oxidation of polyunsaturated fatty acids, resulting in the production of lipid hydroperoxides, which are precursors of inflammatory lipid mediators. These enzymes are widely distributed in humans, other eukaryotes, and cyanobacteria. Lipoxygenases hold promise as therapeutic targets for several human diseases, including cancer and inflammation-related disorders. Inhibitors of lipoxygenase have potential applications in pharmaceuticals, cosmetics, and food. Bioactive peptides are short amino acid sequences embedded within parent proteins, which can be released by enzymatic hydrolysis, microbial fermentation, and gastrointestinal digestion. A wide variety of bioactivities have been documented for protein hydrolysates and peptides derived from different biological sources. Recent findings indicate that protein hydrolysates and peptides derived from both edible and non-edible bioresources can act as lipoxygenase inhibitors. This review aims to provide an overview of the current knowledge regarding the production of anti-lipoxygenase protein hydrolysates and peptides from millet grains, chia seeds, insects, milk proteins, fish feed, velvet antler blood, fish scales, and feather keratins. The anti-lipoxygenase activities and modes of action of these protein hydrolysates and peptides are discussed. The strengths and shortcomings of previous research in this area are emphasized. Additionally, potential research directions and areas for improvement are suggested to accelerate the discovery of anti-lipoxygenase peptides in the near future. Full article
(This article belongs to the Special Issue Bioactive Peptides in Health and Disease)
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