Search Results (52)

Andean crops, including quinoa (Chenopodium quinoa), amaranth species including kiwicha (Amaranthus caudatus), chocho (Lupinus mutabilis), and cañihua (Chenopodium pallidicaule), constitute promising protein matrices for bioactive peptide generation by microbial fermentation and enzymatic proteolysis. These pseudocereals and legumes contain storage proteins, mainly 11S globulins and 2S albumins, enriched in lysine and sulfur-containing amino acids, and therefore provide suitable precursors for multifunctional peptides. In addition, secondary metabolites, such as quinoa saponins and chocho alkaloids, may influence proteolysis, peptide release, and peptide stability during fermentation. This review critically examines LAB fermentation as a food-grade strategy for bioactive peptide production from Andean crops. Evidence from enzymatic hydrolysis and simulated gastrointestinal digestion is included as complementary information and is discussed separately from fermentation-derived evidence. Reported activities include antioxidant, ACE-inhibitory, DPP-IV- and α-glucosidase-inhibitory, antimicrobial and anti-inflammatory activities. Particular attention is given to peptide generation, molecular-weight fractionation, peptidomic characterization, structure–activity relationships, simulated gastrointestinal digestion, and bioaccessibility. Most reported activities were measured in hydrolysates or molecular-weight fractions rather than in defined sequences, and individually validated peptides remain a minority. The strength of evidence differs markedly among crops: fermentation-derived data are more developed for quinoa and amaranth, whereas evidence for chocho and cañihua relies largely on enzymatic hydrolysis. Current limitations, including substrate variability, sensory acceptability, process standardization, peptide identification, bioavailability, and the lack of human validation studies, are also discussed. Andean crop proteins are promising precursors of functional peptide ingredients; however, peptide-specific bioavailability and human efficacy remain largely untested. Full article

Background: Type 2 diabetes (T2DM) is a chronic metabolic disease closely associated with insulin resistance (IR) and disturbances in glucose and lipid metabolism. Bioactive peptides derived from food are attracting increasing research attention as candidates for nutritional supplements or functional food ingredients that improve metabolic health. This study evaluated the functional food-related properties of YPWTQ (CP4), a novel peptide derived from donkey blood, and its ability to alleviate insulin resistance in HepG2 cells. Methods: CP4 was characterized based on its hemolytic activity, stability under simulated gastrointestinal digestion conditions, inhibitory activity against α-glucosidase and Pancreatic lipase, and free radical scavenging capacity (DPPH·, ABTS⁺·, and O₂⁻·). Its effects on glucolipid metabolism and oxidative stress were examined in a glucosamine-induced insulin-resistant HepG2 cell model. Candidate signaling pathways associated with CP4 treatment were explored through transcriptomic and metabolomic analyses, combined with RT-qPCR technology. Results: CP4 exhibited low hemolytic activity and remained stable after 4 h of simulated gastrointestinal digestion. It inhibited α-glucosidase and Pancreatic lipase and exhibited antioxidant activity. In insulin-resistant HepG2 cells, CP4 increased glucose consumption, glycogen content, and cell survival, while reducing triglyceride accumulation, malondialdehyde levels, and reactive oxygen species (ROS) production. Mult omics analysis indicates that these phenotypic effects may be associated with coordinated changes in the PI3K-Akt, AGE-RAGE, Rap1, and Ras signaling pathways, as well as related genes and metabolites. Conclusions: These findings suggest that CP4, as a food-derived bioactive peptide candidate, warrants further investigation into its potential applications in the field of metabolic health. Full article

Coconut kernel fiber (CKF) is a by-product of coconut oil processing; it is rich in protein and serves as a potential source of bioactive peptides. In this study, from the enzymatic hydrolysis products of CKF (CKFH), a low-molecular-weight CKFH component (LW-CKFH, 1–3 kDa), exhibiting 74.49% α-glucosidase inhibition and restoring glucose metabolism in IR-HepG2 cells to 71.37% of normal levels. In a type 2 diabetes (T2DM) mouse model, LW-CKFH alleviated insulin resistance and enhanced insulin sensitivity by repairing liver damage, thereby improving glucose and lipid metabolism and reducing inflammation; its effects on improving insulin resistance and sensitivity reached 75.43% and 75.47% of the efficacy of metformin, respectively. Molecular docking analysis identified FDLPAR, LPFPRPAGPR, and ANVFNPR as key active peptides responsible for inhibiting α-glucosidase activity. Furthermore, LW-CKFH exhibited good gastrointestinal digestibility and processing stability, while significantly reducing the glucose release rate from bread (>50%), indicating its suitability for the development of hypoglycemic or low-GI functional foods. LW-CKFH was particularly suitable as a functional ingredient for fruits, vegetables, grains, and dairy products to develop low-GI or hypoglycemic foods. This study provides new insights into the high-value utilization of the coconut processing by-product CKF. Full article

Natural food-derived proteins are increasingly explored as alternatives to synthetic inhibitors for managing Type 2 diabetes mellitus. Despite the recognized health-promoting properties of Morchella esculenta, the potential of its bioactive proteins to modulate glucose metabolism remains largely unexplored. This study systematically investigated the structural basis and hypoglycemic mechanisms of MEP5 (Morchella esculenta Protein 5), a fucose-specific lectin from M. esculenta, using an integrated in silico pipeline. MEP5 (33.12 kDa) adopts a stable β-sheet-rich conformation and harbors a conserved fucose-binding carbohydrate-recognition domain. Protein–protein docking revealed that intact MEP5 binds directly to surface glycans of human α-glucosidase, generating steric hindrance that obstructs the catalytic pocket. Simulated gastrointestinal digestion yielded a highly bioavailable peptide profile. Following a rigorous multiparametric screening for toxicity, allergenicity, and water solubility, 11 short oligopeptides were identified as potent dipeptidyl peptidase-IV (DPP-IV) inhibitors. Molecular docking demonstrated that the top-ranked peptides, QPPR, DGTY, and DPDSH, occupy the S2 pocket of DPP-IV and form hydrogen bonds with catalytic triad residues (Ser630/His740). These findings delineate a dual-stage hypoglycemic mechanism, pre-digestion enzymatic blockade and post-digestion incretin regulation, and support the potential of MEP5 as a multifunctional candidate for glucose homeostasis-oriented functional foods. Full article

Sea buckthorn leaves are a relatively underutilised component of sea buckthorn processed products; however, various studies have indicated that they possess hypoglycaemic potential. Under alkaline solubilisation and acid-precipitation conditions, the extraction yield of sea buckthorn leaf protein (SLP) reached 19.33%. Trypsin was selected as the hydrolysing enzyme to extract SLPPs-T, with half-maximal inhibitory concentrations (IC₅₀) against α-glucosidase and DPP-IV of 0.1361 ± 0.017 mg/mL and 0.1286 ± 0.012 mg/mL, respectively. UV spectroscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy and particle size analysis indicated that the secondary and microstructures of SLP underwent changes following its hydrolysis to SLPPs-T; following separation, purification, sequence identification and computer screening, two novel peptides, PM-8 and VG-11, were obtained; molecular docking, solid-phase synthesis and in vitro experiments confirmed that VG-11 exhibited superior inhibitory activity, with half-maximal inhibitory concentrations (IC₅₀) against α-glucosidase and DPP-IV of 0.3885 ± 0.015 mM and 0.2611 ± 0.021 mM, respectively. In summary, this study explored the potential of sea buckthorn leaf protein as a natural hypoglycaemic product through a combination of computational modelling and experimental methods, thereby significantly enhancing the value of sea buckthorn resources. Full article

Elaeagnus mollis oilseed (EMO) meal is a protein-rich by-product that may serve as a novel source of food-derived α-glucosidase inhibitory peptides. This study aimed to obtain EMO peptide fractions with enhanced α-glucosidase inhibition and to clarify the activity, stability and mechanism of the most active fraction. Fourteen proteases were compared, and 3.350 acidic protease was selected to establish an optimized hydrolysis process. The resulting EMO hydrolysate showed an IC₅₀ of 9.11 mg/mL against α-glucosidase and no detectable cytotoxicity towards HEK-293T cells at 0.1–12.0 mg/mL. Ultrafiltration yielded four fractions, among which the 3–10 kDa fraction exhibited the highest inhibition and maintained substantial activity under acidic pH (2–6), −20–50 °C, NaCl ≤ 5% and simulated gastrointestinal digestion. Kinetic analysis indicated mixed-type inhibition, while fluorescence, circular dichroism and molecular docking suggested that peptides in this fraction bind near the catalytic site of α-glucosidase and induce local conformational changes. These findings support EMO-derived 3–10 kDa peptides as stable, non-cytotoxic α-glucosidase inhibitors with potential as functional ingredients for dietary management of type 2 diabetes. Full article

This study investigated the α-glucosidase inhibitory potential of enzymatic/alkaline treatments from Palmaria palmata using different proteases and pairwise combinations thereof. Treatments prepared with Alcalase^®, Flavourzyme^®, and Formea^® Prime, alone or in combination, were evaluated for dose-dependent inhibitory activity. Alcalase^®-derived treatments exhibited the highest α-glucosidase inhibition, achieving an IC₅₀ of 2.48 mg·mL⁻¹, outperforming other treatments and combinations. Membrane fractionation of the Alcalase^®-derived treatment into >5 kDa, 3–5 kDa, 1–3 kDa, and <1 kDa fractions revealed a size-dependent trend, with the <1 kDa fraction showing the strongest inhibition (IC₅₀ of 1.94 mg·mL⁻¹). Three peptides, RADIPFRRA, DGIAEAWLG, and FWSQIFGVAF, from the <1 kDa fraction were identified as potential α-glucosidase inhibitors using the BIOPEP-UWM database and were further selected based on a Peptide Ranker score above 0.6 for in silico docking analyses. Docking revealed distinct binding modes: RADIPFRRA and DGIAEAWLG occupied the catalytic cleft, interacting with key residues (Asp518, Asp616, Trp481, Trp613) consistent with competitive inhibition, whereas FWSQIFGVAF bound to a peripheral site, suggesting potential allosteric modulation. Physicochemical analysis further highlighted differences in charge and isoelectric point correlating with their binding behavior. Together, these findings demonstrate that low-molecular-weight peptides derived from P. palmata proteins, particularly those generated by Alcalase^®, possess significant α-glucosidase inhibitory activity, and provide structural insights for the rational design of peptide-based modulators of carbohydrate metabolism. Full article

This study investigated the generation of α-glucosidase inhibitory peptides from whey protein fermented by the marine-derived probiotic Lacticaseibacillus casei DS31 (isolated from the intestinal microbiota of the large yellow croaker, Larimichthys crocea) and assessed their potential for practical glycemic management. Fermentation markedly increased inhibitory activity, with the freeze-dried crude supernatant exhibiting an IC50 of 2.115 mg/mL. Activity was further enriched through stepwise purification: ultrafiltration (<3 kDa) improved potency (IC50 = 1.206 mg/mL), and subsequent Sephadex (crosslinked dextran) G-15 gel filtration yielded a more active E fraction (IC50 = 1.145 mg/mL). LC–MS/MS characterized 19 peptides, and integrated in silico screening (PeptideRanker combined with molecular docking) highlighted GEPGPEGPAG as a leading candidate, showing a more favorable predicted binding energy (−82.50 kcal/mol) than the positive control acarbose (−69.31 kcal/mol). Docking analysis suggests that GEPGPEGPAG may inhibit α-glucosidase by forming a stable network of hydrogen bonds, salt bridges, and hydrophobic interactions within the catalytic pocket. Overall, DS31-fermented whey and its enriched fractions show promise as functional ingredients for postprandial glycemic control. Full article

This study examined whether co-fermentation with Lactobacillus casei CGMCC 15956 and Lactobacillus delbrueckii CGMCC 21287 could enhance the bioactivity of peptides derived from pecan nut cake (PNC) and clarify the underlying mechanisms. The fermented hydrolysate (PNCH) was compared with an unfermented control. PNCH showed higher antioxidant and α-glucosidase inhibitory activities. Total antioxidant capacity increased from 3.17 to 4.81 mM Trolox, and DPPH radical scavenging activity increased from 62.69% to 84.12%. In addition, the IC₅₀ value for α-glucosidase inhibition decreased from 7.549 to 4.509 mg/mL. In a mouse model of acute alcohol-induced liver injury, PNCH significantly alleviated liver damage through the synergistic enhancement of antioxidant and α-glucosidase inhibitory activities. Peptidomic analysis identified two representative bioactive peptides, FAGDDAPR (from actin) and LAGNPDDEFRPQ (from cupin domain–containing protein 1), both of which exhibited antioxidant and α-glucosidase inhibitory activities. Additionally, these peptides alleviated H₂O₂-induced oxidative stress in Caco-2 cells, significantly improving GSH and MDA levels, as well as SOD activity. Molecular docking suggested potential interactions of these peptides with superoxide dismutase, Keap1, and α-glucosidase. These findings support the high-value utilization of PNC and the development of functional peptide-based ingredients. Full article

Type 2 diabetes mellitus (T2DM) poses a critical global health burden, necessitating safer multi-target therapies. We pioneer the exploration of novel bioactive peptides from Tenebrio molitor larvae—an underexplored, sustainable, and edible insect protein—through proteomics-guided screening and bioassays. Six unique peptides (DK-7, WK-6, GR-7, FK-8, SK-6, and DK-8) demonstrated significant α-glucosidase and dipeptidyl-peptidase IV (DPP-IV) inhibitory effects, and significant glucose consumption enhancement in insulin-resistant HepG2 cells. Molecular docking revealed a binding topology where peptides interacted with α-glucosidase at its active sites (Glu271, Arg643, Arg647, Arg653, Tyr733, Lys765, and Glu767) and with DPP-IV at active residues (Phe357, Tyr547, Trp629, Asp729, and Gln731) through dual hydrogen-bond networks and hydrophobic interactions, establishing a novel inhibition mechanism. We wish to propose that insect-derived biopeptides have potential value as next-generation therapeutics, simultaneously advancing sustainable drug discovery and approximating functional food bioresources to biomedicine. Full article

Background and Methods: To address the need for dietary interventions in sub-healthy populations and promote sustainable utilization of agricultural by-products, we isolated Pinus pumila hypoglycemic peptide (PHP) from nut oil meal through enzymatic extraction, ion exchange and gel chromatography purification, and simulated gastric digestion. Results: PHP exhibited significant inhibitory activity against α-amylase and α-glucosidase. In type 2 diabetic mice, PHP significantly ameliorated the “three-more-one-less” syndrome, reduced glycosylated hemoglobin and insulin levels, mitigated liver and kidney tissue lesions, and improved glucose and lipid metabolic disorders—effects partly supported by its enhancement of intestinal barrier function via restoring gut microbiota diversity. Gut microbiota analysis revealed that PHP exerts hypoglycemic effects by regulating gut microbial composition: increasing SCFA-producing taxa, reducing pro-inflammatory/metabolic disorder-associated taxa, and normalizing the Firmicutes/Bacteroidetes ratio. KEGG pathway analysis demonstrated that PHP mediates synergistic hypoglycemic effects by regulating carbohydrate metabolism, amino acid metabolism, and cofactor/vitamin metabolism. Conclusions: This work provides a theoretical foundation for developing natural functional foods from agricultural by-products, supporting PHP’s potential as a dietary supplement for metabolic regulation. 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

Microbial metabolites offer a multitude of mechanisms for alleviating diabetes, particularly type 2 diabetes (T2D). However, the metabolites of yeasts recognised as safe remain under-explored and are receiving less attention in the treatment of T2D. In addition to the recognised probiotic status of certain yeasts, their genetic feature is responsible for many of the effects observed. Branched and non-branched short-chain fatty acids, bioactive peptides, carotenoids, and polysaccharides (β-glucans, mannans, and peptides derived from them) have vital properties that modulate intestinal permeability, soothe inflammation, and directly influence insulin sensitivity. Their action mechanism ranges from hepatic lipogenesis via the induction of hormone-sensitive lipase and the inhibition of α-glucosidase or DPP-IV to promoting the secretion of GLP-1 (Glucagon-Like Peptide-1) and GIP (Gastric Inhibitory Polypeptide), orchestrating immune modulation, and nourishing the gut microbiota. The richness of the yeast metabolome suggests that a concentrated fermentate could be developed to potentiate the functional effects in vitro in the treatment of T2D. The purpose of this review is to take stock of the current state of knowledge of probiotic yeast metabolites and outline their potential for the treatment of diabetes via the development of food supplements or nutraceuticals. Full article

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics. Full article

Moringa oleifera leaf (MOL) and their extracts have been demonstrated to possess hypoglycemic effects in a variety of species, but they are still unknown in dogs. This study examined the effects of Moringa oleifera leaf peptide (MOLP) on α-amylase and α-glucosidase activities. Furthermore, we assessed the impact of MOLP on the estimated glycemic index (eGI) of snacks in vitro and the postprandial glycemic response in dogs. The findings indicated that MOLP exhibited significant inhibitory activities against α-amylase (IC₅₀ = 2.29 ± 0.10 mg/mL) and α-glucosidase (IC₅₀ = 2.80 ± 0.04 mg/mL). Moreover, the MOLP-containing snacks exhibited a lower rate of starch hydrolysis during in vitro digestion, leading to a notable reduction in the eGI when compared to white bread (WB) and control snacks. Incorporating MOLP into snacks causes smoother alterations in postprandial blood glucose, significantly reducing glucose peak, time to peak, and glycemic index (GI). Our findings indicate that MOLP exhibits hypoglycemic potential, offering a scientific foundation for the future development of functional foods aimed at managing diabetes in dogs. Full article