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12 pages, 1676 KiB

Open AccessArticle

A Novel LSTM-Based Machine Learning Model for Predicting the Activity of Food Protein-Derived Antihypertensive Peptides

by Wang Liao, Siyuan Yan, Xinyi Cao, Hui Xia, Shaokang Wang, Guiju Sun and Kaida Cai

Molecules 2023, 28(13), 4901; https://doi.org/10.3390/molecules28134901 - 21 Jun 2023

Cited by 6 | Viewed by 2065

Abstract

Food protein-derived antihypertensive peptides are a representative type of bioactive peptides. Several models based on partial least squares regression have been constructed to delineate the relationship between the structure and activity of the peptides. Machine-learning-based models have been applied in broad areas, which [...] Read more.

Food protein-derived antihypertensive peptides are a representative type of bioactive peptides. Several models based on partial least squares regression have been constructed to delineate the relationship between the structure and activity of the peptides. Machine-learning-based models have been applied in broad areas, which also indicates their potential to be incorporated into the field of bioactive peptides. In this study, a long short-term memory (LSTM) algorithm-based deep learning model was constructed, which could predict the IC₅₀ value of the peptide in inhibiting ACE activity. In addition to the test dataset, the model was also validated using randomly synthesized peptides. The LSTM-based model constructed in this study provides an efficient and simplified method for screening antihypertensive peptides from food proteins. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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7 pages, 1583 KiB

Open AccessCommunication

Collagen-Derived Dipeptide Pro-Hyp Enhanced ATDC5 Chondrocyte Differentiation under Hypoxic Conditions

by Yoshifumi Kimira, Takahiro Sato, Mayu Sakamoto, Yoshihiro Osawa and Hiroshi Mano

Molecules 2023, 28(12), 4664; https://doi.org/10.3390/molecules28124664 - 9 Jun 2023

Cited by 2 | Viewed by 1690

Abstract

Chondrocytes are surrounded by a lower oxygen environment than other well-vascularized tissues with higher oxygenation levels. Prolyl-hydroxyproline (Pro-Hyp), one of the final collagen-derived peptides, has been previously reported to be involved in the early stages of chondrocyte differentiation. However, whether Pro-Hyp can alter [...] Read more.

Chondrocytes are surrounded by a lower oxygen environment than other well-vascularized tissues with higher oxygenation levels. Prolyl-hydroxyproline (Pro-Hyp), one of the final collagen-derived peptides, has been previously reported to be involved in the early stages of chondrocyte differentiation. However, whether Pro-Hyp can alter chondrocyte differentiation under physiological hypoxic conditions is still unclear. This study aimed to investigate whether Pro-Hyp affects the differentiation of ATDC5 chondrogenic cells under hypoxic conditions. The addition of Pro-Hyp resulted in an approximately 18-fold increase in the glycosaminoglycan staining area compared to the control group under hypoxic conditions. Moreover, Pro-Hyp treatment significantly upregulated the expression of SOX9, Col2a1, Aggrecan, and MMP13 in chondrocytes cultured under hypoxic conditions. These results demonstrate that Pro-Hyp strongly promotes the early differentiation of chondrocytes under physiological hypoxic conditions. Therefore, Pro-Hyp, a bioactive peptide produced during collagen metabolism, may function as a remodeling factor or extracellular matrix remodeling signal that regulates chondrocyte differentiation in hypoxic cartilage. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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18 pages, 3724 KiB

Open AccessArticle

Evaluation of Selenomethionine Entrapped in Nanoparticles for Oral Supplementation Using In Vitro, Ex Vivo and In Vivo Models

by Shane Forde, Giulianna Vozza, David J. Brayden, Hugh J. Byrne, Jesus M. Frías and Sinéad M. Ryan

Molecules 2023, 28(7), 2941; https://doi.org/10.3390/molecules28072941 - 25 Mar 2023

Viewed by 1939

Abstract

Selenium methionine (SeMet) is an essential micronutrient required for normal body function and is associated with additional health benefits. However, oral administration of SeMet can be challenging due to its purported narrow therapeutic index, low oral bioavailability, and high susceptibility to oxidation. To [...] Read more.

Selenium methionine (SeMet) is an essential micronutrient required for normal body function and is associated with additional health benefits. However, oral administration of SeMet can be challenging due to its purported narrow therapeutic index, low oral bioavailability, and high susceptibility to oxidation. To address these issues, SeMet was entrapped in zein-coated nanoparticles made from chitosan using an ionic gelation formulation. The high stability of both the SeMet and selenomethionine nanoparticles (SeMet-NPs) was established using cultured human intestinal and liver epithelial cells, rat liver homogenates, and rat intestinal homogenates and lumen washes. Minimal cytotoxicity to Caco-2 and HepG2 cells was observed for SeMet and SeMet-NPs. Antioxidant properties of SeMet were revealed using a Reactive Oxygen Species (ROS) assay, based on the observation of a concentration-dependent reduction in the build-up of peroxides, hydroxides and hydroxyl radicals in Caco-2 cells exposed to SeMet (6.25–100 μM). The basal apparent permeability coefficient (P_app) of SeMet across isolated rat jejunal mucosae mounted in Ussing chambers was low, but the P_app was increased when presented in NP. SeMet had minimal effects on the electrogenic ion secretion of rat jejunal and colonic mucosae in Ussing chambers. Intra-jejunal injections of SeMet-NPs to rats yielded increased plasma levels of SeMet after 3 h for the SeMet-NPs compared to free SeMet. Overall, there is potential to further develop SeMet-NPs for oral supplementation due to the increased intestinal permeability, versus free SeMet, and the low potential for toxicity. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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22 pages, 1580 KiB

Open AccessArticle

Multi-Bioactivity of Protein Digests and Peptides from Oat (Avena sativa L.) Kernels in the Prevention of the Cardiometabolic Syndrome

by Małgorzata Darewicz, Monika Pliszka, Justyna Borawska-Dziadkiewicz, Piotr Minkiewicz and Anna Iwaniak

Molecules 2022, 27(22), 7907; https://doi.org/10.3390/molecules27227907 - 15 Nov 2022

Cited by 11 | Viewed by 2415

Abstract

The aim of this study was to characterize the digests and peptides derived from oat kernel proteins in terms of their major enzyme inhibitory activities related to the prevention of cardiometabolic syndrome. It also entailed the characteristics of antioxidant bioactivity of the analyzed [...] Read more.

The aim of this study was to characterize the digests and peptides derived from oat kernel proteins in terms of their major enzyme inhibitory activities related to the prevention of cardiometabolic syndrome. It also entailed the characteristics of antioxidant bioactivity of the analyzed material. The study was carried out using coupled in silico and in vitro methods. The additional goal was to investigate whether identified peptides can pervade Caco-2 cells. Based on the results of bioinformatic analysis, it was found that the selected oat proteins may be a potential source of 107 peptides with DPP-IV and/or ACE inhibitory and/or antioxidant activity. The duodenal digest of oat kernels revealed multiple activities. It inhibited the activities of the following enzymes: DPP-IV (IC₅₀ = 0.51 vs. 10.82 mg/mL of the intact protein), α-glucosidase (IC₅₀ = 1.55 vs. 25.20 mg/mL), and ACE (IC₅₀ = 0.82 vs. 34.52 mg/mL). The DPPH^• scavenging activity was 35.7% vs. 7.93% that of the intact protein. After in silico digestion of oat proteins, 24 peptides were selected for identification using LC-Q-TOF-MS/MS. Among them, 13 sequences were successfully identified. One of them, i.e., VW peptide, exhibited triple activities, i.e., DPP-IV and ACE inhibitory and DPPH^• scavenging activity. The multifunctional peptides: PW, TF, VF, and VW, were identified in the basolateral samples after transport experiments. Both in silico and in vitro analyses demonstrated that oat kernel proteins were the abundant sources of bioactive digests and peptides to be used in a diet for patients suffering from cardiometabolic syndrome. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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15 pages, 3308 KiB

Open AccessFeature PaperArticle

Tripeptide Leu-Ser-Trp Regulates the Vascular Endothelial Cells Phenotype Switching by Mediating the Vascular Smooth Muscle Cells-Derived Small Extracellular Vesicles Packaging of miR-145

by Tianyuan Song, Minzhi Zhou, Wen Li, Lin Zheng, Jianping Wu and Mouming Zhao

Molecules 2022, 27(20), 7025; https://doi.org/10.3390/molecules27207025 - 18 Oct 2022

Cited by 3 | Viewed by 1819

Abstract

Tripeptide LSW, initially identified as a potent ACE inhibitory peptide from soybean protein, was recently reported to exert a protective effect against angiotensin II-induced endothelial dysfunction via extracellular vesicles (EVs). However, the molecular mechanisms, especially in lipid accumulation-induced atherosclerosis, still remain unclear. The [...] Read more.

Tripeptide LSW, initially identified as a potent ACE inhibitory peptide from soybean protein, was recently reported to exert a protective effect against angiotensin II-induced endothelial dysfunction via extracellular vesicles (EVs). However, the molecular mechanisms, especially in lipid accumulation-induced atherosclerosis, still remain unclear. The study aimed to investigate whether the protective effects of LSW against endothelial dysfunction on vascular endothelial cells (VECs) was via vascular smooth muscle cells (VSMCs)-derived miRNA-145 packaged in EVs. The miRNA-145 was concentrated in EVs from LSW-treated VSMCs (LEVs), internalized into the HVUECs, and targeted the programmed cell death protein 4 (PDCD4) expression of HUVECs. Oxidized low-density lipoprotein (oxLDL) was applied to induce endothelial dysfunction in HUVECs; oxLDL-induced endothelial dysfunction in HUVECs was attenuated by PDCD4 knockout or LEVs incubation. The results of this study suggested a novel function of LSW as a regulator on the functional EVs from vascular cells in the oxLDL-induced atherosclerotic model. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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15 pages, 2930 KiB

Open AccessArticle

Tripeptide IRW Protects MC3T3-E1 Cells against Ang II Stress in an AT2R Dependent Manner

by Nan Shang, Khushwant S. Bhullar and Jianping Wu

Molecules 2022, 27(12), 3684; https://doi.org/10.3390/molecules27123684 - 8 Jun 2022

Viewed by 2193

Abstract

Multiple strategies including the use of bioactive peptides and other nutraceuticals are being adopted to maintain bone health. This study provides an improved and deeper understanding of the pharmacological effects that a bioactive peptide IRW (Ile-Arg-Trp) extends on bone health. Our results showed [...] Read more.

Multiple strategies including the use of bioactive peptides and other nutraceuticals are being adopted to maintain bone health. This study provides an improved and deeper understanding of the pharmacological effects that a bioactive peptide IRW (Ile-Arg-Trp) extends on bone health. Our results showed that IRW treatment protects osteoblasts against Ang II induced decline in cell proliferation and restores protein levels of collagen type I alpha 2 chain (COL1A2) and alkaline phosphatase (ALP) levels in MC3T3-E1 cells (p < 0.05). Apart from augmentation of these mineralization factors, the angiotensin II (Ang II) induced apoptotic stress in osteoblasts was mitigated by IRW as well. At the molecular level, IRW abolished the cytochrome-c release via modulation of pro-and anti-apoptotic genes in MC3T3-E1 cells (p < 0.05). Interestingly, IRW also increased cellular levels of cytoprotective local RAAS factors such as MasR, Ang (1–7), ACE2, and AT2R, and lowered the levels of Ang II effector receptor (AT1R). Further, our results indicated a lower content of inflammation and osteoclastogenesis biomarkers such as cyclooxygenase 2 (COX2), nuclear factor kappa B (NF-κB), and receptor activator of nuclear factor kappa-B ligand (RANKL) following IRW treatment in MC3T3-E1 cells (p < 0.05). The use of an antagonist-guided cell study indicated that IRW contributed to the process of cytoprotection and proliferation of osteoblasts via Runt-related transcription factor 2 (RUNX2) in face of Ang II stress in an AT2R dependent manner. The key findings of our study showed that IRW could potentially have a therapeutic role in the treatment and/or prevention of bone disorders. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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Review

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30 pages, 3991 KiB

Open AccessReview

Depsipeptides Targeting Tumor Cells: Milestones from In Vitro to Clinical Trials

by Plinio A. Trinidad-Calderón, Carlos Daniel Varela-Chinchilla and Silverio García-Lara

Molecules 2023, 28(2), 670; https://doi.org/10.3390/molecules28020670 - 9 Jan 2023

Cited by 6 | Viewed by 2749

Abstract

Cancer is currently considered one of the most threatening diseases worldwide. Diet could be one of the factors that can be enhanced to comprehensively address a cancer patient’s condition. Unfortunately, most molecules capable of targeting cancer cells are found in uncommon food sources. [...] Read more.

Cancer is currently considered one of the most threatening diseases worldwide. Diet could be one of the factors that can be enhanced to comprehensively address a cancer patient’s condition. Unfortunately, most molecules capable of targeting cancer cells are found in uncommon food sources. Among them, depsipeptides have emerged as one of the most reliable choices for cancer treatment. These cyclic amino acid oligomers, with one or more subunits replaced by a hydroxylated carboxylic acid resulting in one lactone bond in a core ring, have broadly proven their cancer-targeting efficacy, some even reaching clinical trials and being commercialized as “anticancer” drugs. This review aimed to describe these depsipeptides, their reported amino acid sequences, determined structure, and the specific mechanism by which they target tumor cells including apoptosis, oncosis, and elastase inhibition, among others. Furthermore, we have delved into state-of-the-art in vivo and clinical trials, current methods for purification and synthesis, and the recognized disadvantages of these molecules. The information collated in this review can help researchers decide whether these molecules should be incorporated into functional foods in the near future. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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18 pages, 694 KiB

Open AccessReview

Food Peptides, Gut Microbiota Modulation, and Antihypertensive Effects

by Patrick Blondin Tsafack, Chen Li and Apollinaire Tsopmo

Molecules 2022, 27(24), 8806; https://doi.org/10.3390/molecules27248806 - 12 Dec 2022

Cited by 5 | Viewed by 3689

Abstract

The gut microbiota is increasingly important in the overall human health and as such, it is a target in the search of novel strategies for the management of metabolic disorders including blood pressure, and cardiovascular diseases. The link between microbiota and hypertension is [...] Read more.

The gut microbiota is increasingly important in the overall human health and as such, it is a target in the search of novel strategies for the management of metabolic disorders including blood pressure, and cardiovascular diseases. The link between microbiota and hypertension is complex and this review is intended to provide an overview of the mechanism including the production of postbiotics, mitigation of inflammation, and the integration of food biological molecules within this complex system. The focus is on hydrolyzed food proteins and peptides which are less commonly investigated for prebiotic properties. The analysis of available data showed that food peptides are multifunctional and can prevent gut dysbiosis by positively affecting the production of postbiotics or gut metabolites (short-chain fatty acids, polysaccharides, biogenic amines, bile acids). Peptides and the postbiotics then displayed antihypertensive effects via the renin-angiotensin system, the gut barrier, the endothelium, and reduction in inflammation and oxidative stress. Despite the promising antihypertensive effect of the food peptides via the modulation of the gut, there is a lack of human studies as most of the works have been conducted in animal models. Full article

(This article belongs to the Special Issue Bioactive Peptides: Emerging Fronts in Nutrition)

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