Search Results (208)

The study presents the potential of milkfish frame, a by-product of milkfish processing, as a source of dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant peptides with potential applications in type 2 diabetes management. Proteomic analysis identified key proteins, including 65 kDa warm temperature acclimation protein 1 and myosin heavy chain. In silico prediction (BIOPEP-UWM) guided the selection of proteases for generating DPP-IV inhibitory peptides. Enzymatic hydrolysates were produced and evaluated for bioactivity. Among the treatments, pepsin hydrolysis (2% v/v, 8 h) yielded the highest peptide content (283.64 mg/g), soluble protein (86.46%), and DPP-IV inhibitory activity (68.47%). The resulting milkfish frame pepsin hydrolysate (MFH) was further enhanced through ultrafiltration and simulated gastrointestinal digestion, which improved the DPP-IV inhibitory and antioxidant capacities. Cytotoxicity assays confirmed that MFH (0–100 μg/mL) was non-toxic to FL83B hepatocytes after 24 h. Moreover, treating TNF-α-induced FL83B cells with 10 μg/mL MFHs improved cell viability, reducing the toxicity induced by TNF-α in cells. These findings show that MFHs exhibit promising antidiabetic potential and could serve as natural alternatives to synthetic drugs for type 2 diabetes management. This also demonstrates the valorization of fish processing by-products into functional food ingredients, advancing sustainable approaches in food innovation. Full article

Dipeptidyl-peptidase IV (DPP4) inhibitors have shown potential anti-tumor properties. This study investigates the therapeutic potential of evogliptin, a DPP4 inhibitor, both as a single agent and in combination with temozolomide (TMZ), in glioma models. In vitro studies were performed using U87 and U373 glioma cell lines exposed to different concentrations of TMZ (250, 500 μM) and evogliptin (250, 500 ng/mL), either alone or together, for 24, 48, and 72 h. Cell viability was determined with the MTT assay. In vivo effectiveness was tested in a xenograft mouse model treated with intraperitoneal injections of evogliptin (60 mg/k g/day), TMZ (15 mg/kg/day), or their combination over 3 weeks. The combination of TMZ and evogliptin markedly reduced cell viability compared to single-agent treatments. DPP4 mRNA levels decreased more substantially with combination therapy. miRNA expression profiling with Affymetrix arrays indicated that certain miRNAs, such as miR-4440 and miR-6780b-5p, were upregulated after treatment with evogliptin or the combination regimen, whereas others were downregulated. These miRNAs could play a role in limiting glioma growth through DPP4 regulation. In the animal model, evogliptin alone did not provide a survival advantage. Analysis of TCGA data showed that glioma patients with decreased DPP4 expression had improved survival rates. The co-administration of evogliptin and temozolomide resulted in distinct miRNA profile changes. Nevertheless, both in vitro and in vivo, the added cytotoxicity from the combination was minimal. Full article

Snack bars are convenient, ready-to-eat foods with various natural ingredients and may serve as functional foods, offering bioactive phytochemicals. In this study, tomato-based snack bars enriched in plant proteins were evaluated for their antioxidant, antidiabetic, anti-obesity, and anti-inflammatory properties by in vitro test, comparing different protein sources (pea and RuBisCO) and drying methods (microwave vacuum and oven). The rubisco bars exhibited the highest levels of polyphenols (10.12 ± 0.27 mg GAE/g) and flavonoids (5.65 ± 0.47 mg CE/g), and demonstrated superior antioxidant capacity in DPPH, ORAC, and FRAP assays, particularly when microwaved. Rubisco bars also exhibited better inhibition activity of dipeptidyl-peptidase IV and pancreatic lipase, suggesting potential antidiabetic and anti-obesity effects. In contrast, pea bars displayed notable anti-inflammatory effects by reducing tumor necrosis factor (TNF)-α-induced cyclooxygenase-2 (COX-2) expression in intestinal cells. Both protein types were digestible, though rubisco bars released more peptides during simulated gastrointestinal digestion. While these in vitro findings provide insights into the functional potential of tomato-based snack bars, further studies, including in vivo investigations, are required to confirm their health-promoting effects and to evaluate physiologically relevant doses. Overall, these findings highlight the potential of tomato-based snack bars as sustainable, nutrient-rich functional foods with potential health-promoting properties. Full article

There is increasing interest in the health-promoting potential of plant protein-derived peptides for managing metabolic disorders. This study investigated the impact of pepsin digestion on pre-hydrolysed versus non-hydrolysed pea protein. Pepsin digestion resulted in a higher degree of hydrolysis in pre-hydrolysed samples (64%) compared to the non-hydrolysed samples (~40%). The pepsin hydrolysates from the pre-hydrolysed protein showed stronger inhibition of key metabolic enzymes compared to non-hydrolysed samples. After ultrafiltration to enrich peptides <10 kDa, inhibition of α-amylase, α-glucosidase, and ACE was markedly enhanced, achieving a maximum of 44.5%, 54% and 95%, respectively. Peptidomic analysis identified unique peptide sequences in the ultrafiltered pre-hydrolysed fraction, in silico prediction confirmed their bioactive potential. These findings demonstrate enhanced bioactivity in pre-hydrolysed pea protein samples following pepsin hydrolysis, which was most evident in the ultrafiltrated fractions. Overall, this approach highlights the relevance of enzymatic hydrolysis and peptide enrichment strategies in developing functional ingredients to support glucose regulation and cardiovascular health. Full article

Biologically active peptides can be obtained with various research methods, depending on the starting material, biological activity, and intended use. To use the most efficient method, it is worth combining in silico and in vitro experiments. Among the tools that can support an in silico analysis are databases such as the Antimicrobial Peptide Database (AMPD) or BIOPEP-UWM. The aim of this study was to make an in silico hydrolysis of peptides with anticancer properties selected from the AMP database, using pepsin, trypsin, and chymotrypsin. Most peptides obtained had properties inhibiting ACE and dipeptidyl peptidase IV activity. Among the resulting peptides, those with the sequence AR, CF, ER, TF, IY, ER, AW, GF, TW, SK and IM are potentially resistant to peptidase from microbial action. An analysis of the peptides’ characteristics showed that peptides with the sequence AR, EK, ER and SK are well-soluble in water and have high affinity for protein and ligand binding. Peptides with the sequence TF, IL and PF are unstable. Thermostable peptides are PGL, IL, GL, IY, VF, PL, IM and QL. The results of the study may be used to design in vitro experiments. Full article

This review highlights the significant therapeutic properties of four indigenous plants in the United Arab Emirates. These include Capparis spinosa L. (family: Capparaceae), commonly known as caper and locally referred to as Kabir; Citrullus colocynthis (L) Schrad. (family: Cucurbitaceae), known in English as bitter apple and locally as Alhanzal; Morus alba L. (family: Moraceae), referred to as white mulberry and locally named Firsad; and Rhazya stricta Decne. (family: Apocynaceae), commonly called harmal-e-shami and known locally as Alhi-rimi. These species are traditionally used for various ethnobotanical purposes and are important components of the region’s flora, such as managing diabetes and associated metabolic disorders. These plants contain diverse bioactive compounds with notable pharmacological activities. For example, caper exhibits antidiabetic effects through flavonoids such as quercetin and kaempferol, which enhance insulin sensitivity and lower blood glucose levels. Bitter apple is rich in cucurbitacins and alkaloids that lower glycated hemoglobin and support pancreatic β-cell function. White mulberry contains chlorogenic acid, rutin, and 1-deoxynojirimycin, which improve glucose uptake, inhibit α-glucosidase, and reduce oxidative stress. Harmal-e-shami exhibits variable antidiabetic activity, including dipeptidyl peptidase-IV inhibition and enhancement of glucagon-like peptide-1 secretion, which is influenced by the type and dosage of the extract. Despite these promising effects, challenges remain in standardization, phytochemical variability, and clinical validation. This review underscores the therapeutic potential of these plants and recommends further research for their integration into sustainable, plant-based diabetes management strategies. Full article

Sesame oil extraction byproduct (SOEB) contains a high percentage of protein (49.81 g/100 g), making it a suitable plant-based source for producing protein hydrolysates with nutraceutical potential. In this study, albumins, globulins, glutelins, and prolamins fractions were extracted and characterized from SOEB. These fractions were then enzymatically hydrolyzed with alcalase, yielding high soluble protein content (>90%) and hydrolysis degrees ranging from 34.66 to 45.10%. The hydrolysates were fractionated by molecular weight (<5 kDa, 3–5 kDa, 1–3 kDa, and <1 kDa). These fractions demonstrated potential for inhibiting the DPPH radical (25.19–95.79%) and the α-glucosidase enzyme (40.14–55.63%), particularly the fractions with molecular weight <1 kDa. We identified 28 peptides, with molecular weights between 332.20 and 1096.63 Da, which showed potent antioxidant activities (IC₅₀ = 90.18 µg/mL), as well as inhibitory effects on key enzymes such as α-glucosidase (IC₅₀ = 61.48 µg/mL), dipeptidyl peptidase IV (IC₅₀ = 12.12 µg/mL), and pancreatic lipase (IC₅₀ = 6.14 mg/mL). These results demonstrate the antioxidant, antihyperglycemic, antidiabetic, and anti-obesity potential of SOEB peptides, highlighting their use in the formulation of new functional foods or nutraceuticals. Full article

Dry-cured ham is a traditional food in the Mediterranean diet, which, in addition to its sensory qualities, is a natural source of bioactive peptides generated during the curing process through the action of endogenous enzymes on muscle and sarcoplasmic proteins. These low-molecular-weight peptides have attracted growing interest due to their multiple bioactivities, including antihypertensive, antioxidant, antimicrobial, antidiabetic, and anti-inflammatory effects described in vitro, in vivo, and in preliminary human studies. The identification of specific sequences, such as AAPLAP, KPVAAP, and KAAAAP (ACE inhibitors), SNAAC and GKFNV (antioxidants), RHGYM (antimicrobial), and AEEEYPDL and LGVGG (dipeptidyl peptidase-IV and α-glucosidase inhibitors), has been possible thanks to the use of peptidomics techniques, tandem mass spectrometry, and bioinformatics tools that allow their activity to be characterized, their digestive stability to be predicted, and their bioavailability to be evaluated. This review article summarizes current knowledge on the bioactivities of peptides derived from dry-cured ham, advances in their functional characterization, and challenges associated with their application in functional foods and nutraceuticals, with the aim of providing a comprehensive overview of their potential in health promotion and chronic disease prevention. Full article

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are among the most widespread drugs for the prevention of cardiovascular mortality and morbidity. Nevertheless, they are known to cause bradykinin (BK)-mediated angioedema (AE), a paroxysmal, localized, self-limiting, and potentially fatal swelling of the subcutaneous and/or submucosal tissue, due to a temporary increase in vascular permeability. Unlike hereditary angioedema (HAE), which can be mediated similarly by BK, no diagnostic tools, guidelines, or drugs have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced AE. Besides ACEIs and ARBs, inhibitors of dipeptidyl peptidase-IV, neprilysin inhibitors, and tissue plasminogen activators are known to cause AE as an adverse effect. Currently, there are insufficient data on the prevention of AE caused by pharmacological therapies. In addition, the molecular mechanisms underlying BK-mediated AE caused by drugs, which are discussed here, are not fully explained. Specific approved drugs and a structured diagnostic workflow are unmet needs and are required for the management of this kind of AE. The aim of this review is to provide physicians with accurate knowledge of potentially life-threatening drug reactions so that they can be better understood and managed. Full article

Background/Objectives: Essential amino acid (EAA) supplementation is often employed in sportive and clinical nutrition due to EAAs’ role in muscle mass maintenance and growth. EAAs are also involved in insulin and glucagone regulation in diabetes management, but only few reports investigate their possible implication as dipeptidyl peptidase-IV (DPP-IV) inhibitors and their effect on the stability and secretion of enteroendocrine hormones. A blend of EAAs (called GAF) available as a food supplement, in a specific qualitative and quantitative ratio, was investigated to address its in vitro bioaccessibility, its hypoglycemic properties in vitro and in situ on cellular models, and its safety on intestinal Caco-2 cells. Methods: GAF was subjected to the INFOGEST static digestion protocol, producing the iGAF sample. iGAf DPP-IV inhibitory properties were investigated both in vitro and in situ on Caco-2 cells. Then, STC-1 enteroendocrine cells were employed alone and in co-culture with Caco-2 cells to evaluate iGAF’s impact on glucagon-like peptide 1 (GLP-1) hormone secretion. Results: The study demonstrates that the present EAAs blend is stable and bioaccessible after simulated gastrointestinal digestion, and it is safe at the intestinal cellular level. It inhibits DPP-IV enzyme both in vitro and in situ and promotes GLP-1 secretion by enteroendocrine cells. Conclusions: The sample demonstrated safety at the intestinal level and showed hypoglycemic properties by acting on a dual synergic mechanism that involves DPP-IV enzyme inhibition and GLP-1 hormone stimulation. Full article

Chicken feathers constitute a major by-product from the poultry industry, with a potential environmental impact and significant difficulties in their management. This study aimed to develop a sustainable method to hydrolyse chicken feathers and evaluate the effects of microwave (MW) irradiation pre-treatment in the generation of bioactive hydrolysates by simple or sequential hydrolysis with Alcalase. The hydrolysate with MW irradiation pre-treatment and Alcalase (2%, 2 h) (MWA) showed the highest overall antioxidant activity and neprilysin-inhibitory activity (55%), whereas samples without MW irradiation pre-treatment exerted the highest inhibitory activity of dipeptidyl peptidase IV (DPP IV) and angiotensin-converting enzyme (ACE-I), with values close to 50 and 70%, respectively. Mass spectrometry in tandem of bioactive hydrolysates was performed, and an in silico approach was used to characterise the obtained sequences. These results confirmed that MW irradiation pre-treatment improved Alcalase hydrolysis, leading to the generation of bioactive peptides with potential multifunctional properties, including antioxidant, antidiabetic, and antihypertensive activities. Moreover, this study highlights the potential of combining MW irradiation and enzymatic hydrolysis as a sustainable strategy for the revalorisation of chicken feathers. Full article

Goat caseins are highly polymorphic proteins that affect milk functional properties. In this study, an in silico approach was employed to analyze the influence of goat casein allelic variants on the quantity and bioactivity potential of peptides released after enzymatic hydrolysis. The reported protein sequences from the most frequent allelic variants in Capra hircus caseins (α-S1, β, α-S2, and κ-casein) were analyzed in the BIOPEP-UWM database to determine the frequency of occurrence of bioactive fragments from each casein. After specific hydrolysis with pepsin, trypsin, and chymotrypsin A, important differences in the peptide profile and bioactivity potential were observed within and between the casein allelic variants. The β-casein A and C alleles, α-S1-casein allele E, and α-S2-casein allele F presented the highest bioactivity potential, and some allele-specific peptides were also released, highlighting the impact of genotype on the predicted bioactivity. The inhibition of angiotensin-converting enzyme (ACE-I) and dipeptidyl peptidase IV (DPP-IV) activities was the most frequent bioactivity of the released peptides, suggesting possible antihypertensive and antidiabetic effects. Once confirmed by experimental studies, the use of goat casein genotyping could direct efforts to enhance the functional quality of goat milk. Full article

Sheep milk is a rich source of bioactive compounds with significant potential in functional foods and biomedical applications. It contains high levels of proteins, peptides, and fatty acids with numerous health-promoting properties for the human body. Key components such as lactoferrin, proline, orotic acid, and conjugated linoleic acid (CLA) support the prevention and treatment of chronic diseases such as diabetes, cardiovascular disease, obesity, cancer, and neurodegenerative disorders. Bioactive peptides from sheep milk regulate blood glucose levels by inhibiting enzymes such as dipeptidyl peptidase-IV (DPP-IV) and α-glucosidase, while conjugated linoleic acid improves lipid metabolism and reduces inflammation. The high-quality proteins in sheep milk are essential for tissue regeneration and maintaining muscle mass, which is particularly beneficial for the elderly and infants who are allergic to cow milk. Recently, there has been an increasing interest in hydrogel dressings enriched with bioactive substances from sheep milk, which support wound healing by supporting collagen synthesis, reducing inflammation, and having antimicrobial properties. Such hydrogels are particularly promising for the treatment of chronic wounds, burns, and diabetic ulcers, making them a valuable tool in regenerative medicine. The aim of this manuscript is to review the current reports on bioactive components of sheep milk and their potential for biomedical applications. Full article

Type 2 diabetes mellitus (T2DM) is a complex and prevalent metabolic disorder, and dipeptidyl peptidase 4 (DPP4) inhibitors have proven effective, yet the identification of novel inhibitors remains challenging due to the vastness of chemical space. In this study, we developed DPPPRED-IV, a web-based ensembled system integrating both binary classification and continuous regression Quantitative Structure Activity Relationships (QSAR) models to predict human DPP4 inhibitory activity. A curated dataset of 4 676 ChEMBL compounds was subjected to genetic algorithm descriptor selection and multiple machine learning algorithms; classification models were combined via a soft voting ensemble, while regression models estimated IC₅₀ values. All models underwent external 10-fold cross-validation and applicability domain analysis. The final models were integrated into a user-friendly web server, allowing predictions from SMILES inputs. Experimental testing of 29 MolPort compounds at 1.5 µM confirmed that 14 predicted actives exhibited significant inhibition, supporting the tool’s performance in early-stage screening. DPPPRED IV is freely available within the ChemoPredictionSuite and offers a resource to accelerate decision making, reduce costs and minimize animal use in T2DM drug discovery. Full article

Type 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week period. Glucose tolerance was evaluated via oral glucose tolerance tests (OGTT), while plasma dipeptidyl peptidase-IV (DPP-IV) activity, glucagon-like peptide-1 (GLP-1), and insulin concentrations were quantified using enzyme-linked immunosorbent assays (ELISA). Two bioactive peptides, GPFPLPD and APDSGNFR, were isolated and characterized, exhibiting half-maximal inhibitory concentrations (IC₅₀) of 99.12 µM and 73.07 µM for DPP-IV inhibition, respectively, and both significantly stimulated GLP-1 secretion in enteroendocrine cells in vitro. Pharmacokinetic analysis in Sprague–Dawley rats demonstrated oral bioavailability of 11.28% and 19.12% for these peptides, surpassing typical expectations for peptide-based agents. Collectively, these results provide compelling evidence that 1CBR-derived peptides exert glucose-lowering effects through the dual mechanisms of DPP-IV inhibition and GLP-1 stimulation, combined with favorable oral absorption profiles. These findings underscore the potential of 1CBR peptides as promising candidates for development into nutraceuticals or pharmaceutical agents for diabetes management. Full article