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This study investigates the production of protein hydrolysates with dipeptidyl peptidase-IV (DPP-IV) inhibitory activity from agro-industrial by-products, namely olive seed, sunflower seed, rapeseed, and lupin meals, as well as from two plant protein isolates such as pea and potato. Furthermore, the effect of simulated gastrointestinal digestion on the DPP-IV inhibitory activity of all the hydrolysates was evaluated. Overall, the lowest values of IC50 (1.02 ± 0.09–1.24 ± 0.19 mg protein/mL) were observed for the hydrolysates with a high proportion of short-chain [<1 kDa] peptides (i.e., olive seed, sunflower seed, and lupin) or high content of proline (i.e., rapeseed). Contrarily, the IC50 of the pea and potato hydrolysates was significantly higher (1.50 ± 0.13–1.93 ± 0.13 mg protein/mL). In vitro digestion led to an increase in peptides < 1 kDa for almost all hydrolysates (except olive and sunflower seed meals), which was noticeable for rapeseed, pea, and potato hydrolysates. Digestion did not significantly modify the DPP-IV inhibitory activity of olive, sunflower, rapeseed, and potato hydrolysates, whereas a significant decrease in IC50 value was obtained for pea hydrolysate and a significant increase in IC50 was obtained for lupin hydrolysate. Thus, this work shows the potential of agro-industrial by-products for the production of protein hydrolysates exhibiting DPP-IV inhibition. [ABSTRACT FROM AUTHOR]

Summary: The aim of the present study was to follow the dynamics of potential antihypertensive (angiotensin‐converting enzyme (ACE)) and antidiabetogenic (dipeptidyl peptidase IV (DPP‐IV)) inhibitory activities during artisanal fermentation of Mexican cocoa beans. Almendra Blanca, Criollo and Forastero cocoa beans were sampled after 0, 48, 72, 96 and 120 h of fermentation and roasting (140 °C) and subjected to simulated gastrointestinal digestion. Subsequently, proteolytic activity (OPA method), peptide abundance (RP–HPLC), ACE and DPP‐IV inhibitory activities and IC50 were determined. The results showed that proteolytic activity, peptide abundance and ACE and DPP‐IV inhibition were higher (P < 0.05) at the final stages of fermentation (96 and 120 h). However, IC50 values in partially fermented (48 to 96 h) cocoa beans were the lowest (P < 0.05) of all. In conclusion, a partially fermented cocoa bean may be desirable for its use as a functional ingredient with potential antihypertensive and antidiabetogenic effects. [ABSTRACT FROM AUTHOR]

Metabolic disorders are increasingly prevalent conditions that manifest pathophysiologically along a continuum. Among reported metabolic risk factors, elevated fasting serum glucose (FSG) levels have shown the most substantial increase in risk exposure. Ultimately leading to insulin resistance (IR), this condition is associated with notable deteriorations in the prognostic outlook for major diseases, including neurodegenerative diseases, cancer risk, and mortality related to cardiovascular disease. Tackling metabolic dysfunction, with a focus on prevention, is a critically important aspect for human health. In this study, an investigation into the potential antidiabetic properties of a salmon protein hydrolysate (SPH) was conducted, focusing on its potential dipeptidyl peptidase-IV (DPP-IV) inhibition and direct glucose uptake in vitro. Characterization of the SPH utilized a bioassay-guided fractionation approach to identify potent glucoregulatory peptide fractions. Low-molecular-weight (MW) fractions prepared by membrane filtration (MWCO = 3 kDa) showed significant DPP-IV inhibition (IC50 = 1.01 ± 0.12 mg/mL) and glucose uptake in vitro (p ≤ 0.0001 at 1 mg/mL). Further fractionation of the lowest MW fractions (<3 kDa) derived from the permeate resulted in three peptide subfractions. The subfraction with the lowest molecular weight demonstrated the most significant glucose uptake activity (p ≤ 0.0001), maintaining its potency even at a dilution of 1:500 (p ≤ 0.01). [ABSTRACT FROM AUTHOR]

An attempt was made to produce hydrolysates from β‐casein isolated from milk of Gir cow (Bos indicus species) using pepsin, trypsin, protease from Aspergillus oryzae (AOP) and proteinase‐K. The AOP‐treated hydrolysates exhibited highest DPP‐IV inhibition (50.41 ± 1.44%) after 10 h hydrolysis at 4% E:S ratio. The resultant hydrolysates were characterised using RP‐HPLC and LC–MS/MS and their peptides sequences identified. The efficacy of the low molecular weight hydrolysates (3 kDa permeate) was assessed through MIN6 cell line model at different doses. The dose of 30 mg/mL enhanced insulin production by ~51% and reduced the apoptosis by ~84%. The developed β‐casein hydrolysates could be used as a dietary supplement to manage diabetes effectively. [ABSTRACT FROM AUTHOR]

This work analyzed the antidiabetic activity of peptides from whey proteins after hydrolysis by Lactobacillus rhamnosus GG and Streptococcus thermophilus SY-102, emphasizing the differences between the proteolytic systems of both bacteria. Peptide fractions from whey proteins may have biological functions, such as antidiabetic functions, which inhibit the DPP-IV enzyme, and lactic acid bacteria could release them. A whey solution of 10% was fermented with selected lactic acid bacteria in monoculture and coculture, analyzing kinetic parameters and the proteolytic profile, using the 2,4,6-trinitrobenzene sulfonic acid technique for free amino groups’ determination and Tris-tricine polyacrylamide gel electrophoresis. An in vitro inhibition assay of the DPP-IV enzyme was used. The kinetic parameters showed a faster duplication rate in the monoculture with L. rhamnosus GG than in the co-culture, which was related to lactic acid production. Co-culture does not have the highest production of free amino groups and peptides. Still, peptide fractions with lower molecular weight (L. rhamnosus GG increased from 0 to 63.3%. This demonstrates that the proteolytic capacity and the proteolytic system of each lactic acid bacteria determine the structure of the released peptides.

This study investigates the production of protein hydrolysates with dipeptidyl peptidase-IV (DPP-IV) inhibitory activity from agro-industrial by-products, namely olive seed, sunflower seed, rapeseed, and lupin meals, as well as from two plant protein isolates such as pea and potato. Furthermore, the effect of simulated gastrointestinal digestion on the DPP-IV inhibitory activity of all the hydrolysates was evaluated. Overall, the lowest values of IC50 (1.02 ± 0.09 – 1.24 ± 0.19 mg protein/mL) were observed for the hydrolysates with a high proportion of short-chain [< 1 kDa] peptides (i.e., olive seed, sunflower seed, and lupin) or high content of proline (i.e., rapeseed). Contrarily, the IC50 of the pea and potato hydrolysates was significantly higher (1.50 ± 0.13 – 1.93 ± 0.13 mg protein/mL). In vitro digestion led to an increase in peptides 50 value was obtained for pea hydrolysate and a significant increase in IC50 was obtained for lupin hydrolysate. Thus, this work shows the potential of agro-industrial by-products for the production of protein hydrolysates exhibiting DPP-IV inhibition.

Summary: The present research aimed to evaluate three peptides synthesised from tarwi: AVPFWM, YSGWLGL and AHAGFGMLY in their antioxidant, antihypertensive and hypoglycemic properties, using in vitro and in silico studies, this last one considering the molecular docking evaluation and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties. The in vitro results found ABTS and ORAC antioxidant capacity values between 2.12 and 3.94 and 1.64 and 3.10 μmol TE/μmol of peptide, respectively, while the IC50 values for angiotensin‐converting enzyme (ACE) and dipeptidyl peptidase IV (DPP‐IV) inhibition ranged between 0.14 and 6.38 μM and 16.4 and 1140.0 μM, respectively. The molecular docking study performed between peptides and ACE and DPP‐IV enzymes, showed affinity towards both enzymes establishing molecular interactions at the level of the active site of both enzymes through hydrogen bonds and hydrophobic interactions. This study together with the in vitro study highlight the YSGWLGL peptide for the favourable results found. Finally, the predicted ADMET properties of the three peptides suggest that they have the potential for absorption, appropriate distribution, no participation in the metabolism of P450 enzymes and no toxicity concerns. It is concluded that tarwi peptides may be a valuable source for developing nutraceuticals, functional ingredients or supplements. [ABSTRACT FROM AUTHOR]

This work analyzed the antidiabetic activity of peptides from whey proteins after hydrolysis by Lactobacillus rhamnosus GG and Streptococcus thermophilus SY-102, emphasizing the differences between the proteolytic systems of both bacteria. Peptide fractions from whey proteins may have biological functions, such as antidiabetic functions, which inhibit the DPP-IV enzyme, and lactic acid bacteria could release them. A whey solution of 10% was fermented with selected lactic acid bacteria in monoculture and coculture, analyzing kinetic parameters and the proteolytic profile, using the 2,4,6-trinitrobenzene sulfonic acid technique for free amino groups' determination and Tris-tricine polyacrylamide gel electrophoresis. An in vitro inhibition assay of the DPP-IV enzyme was used. The kinetic parameters showed a faster duplication rate in the monoculture with L. rhamnosus GG than in the co-culture, which was related to lactic acid production. Co-culture does not have the highest production of free amino groups and peptides. Still, peptide fractions with lower molecular weight (<2 kDa) were found and showed a high DPP-IV inhibitory capacity that was maintained from the middle of the fermentation to the end (55.4%). In comparison, the monoculture of L. rhamnosus GG increased from 0 to 63.3%. This demonstrates that the proteolytic capacity and the proteolytic system of each lactic acid bacteria determine the structure of the released peptides. [ABSTRACT FROM AUTHOR]

Metabolic disorders are increasingly prevalent conditions that manifest pathophysiologically along a continuum. Among reported metabolic risk factors, elevated fasting serum glucose (FSG) levels have shown the most substantial increase in risk exposure. Ultimately leading to insulin resistance (IR), this condition is associated with notable deteriorations in the prognostic outlook for major diseases, including neurodegenerative diseases, cancer risk, and mortality related to cardiovascular disease. Tackling metabolic dysfunction, with a focus on prevention, is a critically important aspect for human health. In this study, an investigation into the potential antidiabetic properties of a salmon protein hydrolysate (SPH) was conducted, focusing on its potential dipeptidyl peptidase-IV (DPP-IV) inhibition and direct glucose uptake in vitro. Characterization of the SPH utilized a bioassay-guided fractionation approach to identify potent glucoregulatory peptide fractions. Low-molecular-weight (MW) fractions prepared by membrane filtration (MWCO = 3 kDa) showed significant DPP-IV inhibition (IC50 = 1.01 ± 0.12 mg/mL) and glucose uptake in vitro (p ≤ 0.0001 at 1 mg/mL). Further fractionation of the lowest MW fractions (p ≤ 0.0001), maintaining its potency even at a dilution of 1:500 (p ≤ 0.01).

Background: Developing value‐added products from rice grains is becoming increasingly significant to enhance productivity from excess rice grains. Therefore, the objective of this study was to improve the functional properties of rice protein from four rice varieties, namely, RRF‐127, RRF‐105, Swarna, and Protezin by enzymatic hydrolysis, and also to evaluate bioactivities like antioxidant, ACE, and DPP‐IV inhibitory activities of the hydrolysates. Results: The alcalase hydrolysis increased protein solubility to >80% in the pH range of 4–10. The foaming capacity and stability of rice protein hydrolysates (RPHs) improved with the increase in pH. The hydrolysis significantly improved the emulsification activity index (EAI) in the pH range of 5–9. The hydrolysates showed antioxidant activity, namely, ABTS•+radical scavenging, reducing power, and metal ion chelation. RRF‐105 was found to possess the most potent antioxidant capacity among the hydrolysates. RPH could alleviate oxidative damage in erythrocytes, and their protective effects were concentration‐dependent. The hydrolysates had stronger inhibition of ACE and DPP‐IV enzymes. Protezin exhibited the highest ACE inhibition (63%), while Swarna demonstrated the most effective DPP‐IV inhibition (66%). Conclusion: Hydrolysis with alcalase improved the functional and bioactive properties of rice proteins, indicating that RPH could serve as a source of bioactive peptides or as a functional ingredient with potential properties. [ABSTRACT FROM AUTHOR]

The multifactorial nature of type 2 diabetes mellitus (T2DM) has driven a need to discover multifunctional antidiabetic peptides preferably from functional food sources for possible application as antidiabetic supplements. Herein, the antidiabetic effects of bioactive peptides previously identified in yam (AVIAIMF & GPADPF) and taro (NGDF & NGNW) were investigated. The peptides showed significantly (p < 0.05) higher dipeptidyl peptidase IV inhibitory activities than vildagliptin with NGDF having the best activity. AVIAIMF, GPADPF, and NGNW significantly inhibited the formation of methylglyoxal-induced advanced glycosylated end products (AGEs) while AVIAIMF and NGNW showed oxygen radical scavenging (ORAC) activities. The peptides also showed significant (p < 0.05) nitric oxide (NO) scavenging activities in murine macrophage (RAW 264.7) cells and were not cytotoxic to the RAW 264.7 cells in the presence and absence of lipopolysaccharide. The peptides did not show a biologically significant inhibition of lipid formation in 3T3-LI adipocytes and were not cytotoxic to human colon adenocarcinoma (Caco-2) cells, suggesting safety. The ORAC negatively correlated (− 0.40) with % AGEs formed and positively correlated (0.53 and 0.41) with the viability of LPS + and LPS- RAW 264.7 cells respectively. AVIAIMF, GPADPF and NGNW have shown promising multifunctional anti-T2DM activities that could be considered as potential antidiabetic peptides for application in functional antidiabetic foods. [ABSTRACT FROM AUTHOR]

The impact of whey protein (WP) denaturation on the in vitro digestibility and biological activity of milk protein concentrate-85 (MPC85) was investigated. MPC85S1 and MPC85S2 having undenatured WP levels equal to 16.6 and 6.0 g/100 g overall protein, respectively, had similar in vitro protein digestibility corrected amino acid scores equal to 1.14. The samples were subjected to in vitro simulated gastrointestinal digestion while sampling was performed every 30 min during gastric (GD) followed by intestinal (GID) digestion. Liquid chromatography–mass spectroscopy showed that MPC85S1-GD, MPC85S2-GD, MPC85S1-GID and MPC85S2-GID had 50, 38, 47 and 66 unique peptides, respectively. The degree of hydrolysis, molecular mass distribution, dipeptidyl peptidase-IV inhibition, oxygen radical absorbance capacity and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity of the digests were compared. Overall, the results showed higher digestibility and bioactivities for low-denatured MPC85 compared to high-denatured MPC85 upon GD, however, following GID, both samples were digested to a similar extent.

Press cakes are by-products of cold press oil manufacture and are characterized by significant protein concentrations. Our group has previously demonstrated potential bioactive attributes of hazelnut protein hydrolysates including their antidiabetic activities. Here, an effort was made to utilize DPP-IV (Dipeptidyl peptidase-IV)-inhibitory hazelnut peptides in industrial food manufacture. Hazelnut protein isolates (approx. 95% protein) were obtained via an alkali extraction-isoelectric precipitation method. Papain, bromelain and pepsin were used in the enzymatic hydrolysis and hydrolysates were fractionated via Fast Protein Liquid Chromatography. As a general observation, although fractionation lead to dilution of the samples, fractions were observed to be more bioactive than the total hydrolysates. In vitro antidiabetic activities of the fractions were tested and 3 antidiabetic fractions were added to hazelnut paste. Afterwards simulated gastrointestinal digestion and antidiabetic activity assays were performed. DPP-IV inhibition was the major antidiabetic mechanism in the fractions and digested paste, while some fractions were characterized by comparable IC50 values as the positive controls. Alpha-glucosidase inhibition was limited by digestion trials, whereas alpha-amylase inhibition was only slight in the digested paste (< %6). In silico analyses predicted partial degradation of the peptides, whereas the interactions between DPP-IV or alpha-glucosidase and hazelnut peptides were predicted to be significant (p < 0.05). Consequently hazelnut press cakes were regarded as a potential source of antidiabetic peptides that can be used in industrial manufacture of functional foods, while food processing conditions or gastrointestinal digestion could largely affect peptide bioactivity. [ABSTRACT FROM AUTHOR]

An attempt has been made to assess the dipeptidyl peptidase‐IV (DPP‐IV) inhibitory potential of α‐lactalbumin separated from milk of Gir cow. α‐lactalbumin hydrolysates were prepared using three different enzymes at different enzyme‐to‐substrate (E:S) ratios (1:25, 1:50 and 1:100) treated for 2‐ to 12‐h durations. Pepsin‐treated hydrolysates showed maximum DPP‐IV inhibition of 87.81 ± 0.84% (IC50 = 0.78 mg/mL). The permeate of 3 kDa, which exhibited 84.47 ± 2.29% DPP‐IV inhibition, was fractionated through RP‐HPLC. All fractions were analysed for DPP‐IV inhibition activity. One novel peptide was identified through LC‐MS/MS, which showed adequate DPP‐IV inhibition (IC50 = 4.93 mM). [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides exhibit great potential to alleviate type II diabetes. This study aimed to prepare, identify and explore the molecular mechanism of DPP-IV inhibitory peptides from eggshell membrane (ESM), an abundant byproduct of the food industry, based on combining in silico and in vitro assessments. In silico evaluation of ten major ESM proteins revealed the great potential of ESM as a novel source of DPP-IV inhibitors. Moreover, the optimal combined-enzymatic strategy (alkaline protease + papain) for the efficient production of DPP-IV inhibitory peptides from ESM was designed by simulated proteolysis. Corresponding with in silico predictions, in vitro assessments confirmed that sodium sulfite assisted the screened dual enzymes led to better production of DPP-IV inhibitory peptides from ESM, with preferable total nitrogen recovery (86.61% ± 4.83%), DPP-IV inhibitory activity (64.61% ± 2.75%) and total antioxidant activity (215.27 ± 1.75 μg/mL). Due to the correlation between diabetes and oxidative stress, the antioxidant and DPP-IV inhibitory activities of the hydrolysate facilitate its amelioration of diabetes. Three novel DPP-IV inhibitory peptides with high abundance in ESM hydrolysates (YPEPPPQ, HDGADVS and VTDGQPH) were identified by LC-MS/MS, in silico characterization and molecular docking. These peptides were synthesized and confirmed to possess DPP-IV inhibitory activity, potentially relating to their stable binding with key residues within the S1, S2 pockets and catalytic triad of DPP-IV via hydrogen bonding and hydrophobic interaction. Overall, this research suggests an effective and time-saving strategy to investigate novel DPP-IV inhibitory peptides from ESM, as well as opens new opportunities for ESM application in antidiabetic foods. [Display omitted] • The discarded Eggshell membrane (ESM) is a novel source of DPP-IV inhibitory peptides. • In silico analysis provides guidance for in vitro exploration of ESM-derived peptides. • Na 2 SO 3 -assisted dual enzymatic hydrolysis was optimal for releasing DPP-IV inhibitors. • Three novel peptides were identified and validated experimentally the bioactivity. • H-bonds and hydrophobic interactions with DPP-IV were the key interaction modes. [ABSTRACT FROM AUTHOR]

This work studied the effects of gastrointestinal digestion on the phytochemical bioaccessibility and in vitro anti‐diabetic effects of different fractions from Chinese sumac fruits and delineated the underlying mechanisms by molecular docking. Results showed that gastric digestion significantly increased the phytochemical bioaccessibility and inhibitions for α‐glucosidase, dipeptidyl peptidase‐4 (DPP‐IV) and advanced glycation end product (AGE) formation of the ethanol‐extracted fraction, whereas intestinal digestion remarkably decreased these parameters (P < 0.05). For the free phenolic fraction, the parameters were remarkably reduced after gastric digestion but significantly increased after intestinal digestion (P < 0.05). Quercitrin and gvajaverin contributed the most to the α‐glucosidase and DPP‐IV inhibitions, and trigalloyl glucose and its isomer could be the primary bioactive substance responsible for AGE suppression. Quercitrin, the predominant phenolic compound, could effectively interact with crucial amino acid residues in α‐glucosidase, DPP‐IV and bovine serum albumin with hydrogen bonds and hydrophobic interactions to exert its inhibitions. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, particularly type 2 diabetes, is a major global health issue, the prevalence of which seems to be on the rise worldwide. Interventions such as healthy diet, physical activity, maintaining a healthy weight, and medication (for those with a diagnosis of diabetes) are among the most effective strategies to prevent and control diabetes. Three-quarters of patients diagnosed with diabetes are in countries with poor financial infrastructure, nutritional awareness and health care systems. Concomitantly, the cost involved in managing diabetes through the intake of antidiabetic drugs makes it prohibitive for majority of patients. Food protein-derived bioactive peptides have the potential of being formulated as nutraceuticals and drugs in combating the pathogenesis and pathophysiology of metabolic disorders with little or "no known" complications in humans. Coupled with lifestyle modifications, the potential of bioactive peptides to maintain normoglycemic range is actualized by influencing the activities of incretins, DPP-IV, α-amylase, and α-glucosidase enzymes. This article discusses the biofunctionality and clinical implications of anti-diabetic bioactive peptides in controlling the global burden of diabetes. [ABSTRACT FROM AUTHOR]

The current study reported oat protein as a precursor for α-amylase, α-glucosidase, and dipeptidyl peptidase (DPP)-IV inhibitory peptides and studied the antidiabetic activities related to their structures. Enzyme inhibition assays in vitro, using oat protein treated by alcalase and flavourzyme fractionated into different molecular weights and hydrophobicity, indicated that the relatively hydrophobic fraction of 1–5 kDa inhibited enzymes related to glucose digestion, absorption, and metabolism activities. The α-amylase and DPP-IV were inhibited 57 and 78%, respectively, even at low peptide concentrations. LC-MS/MS analysis of the most effective fractions disclosed two eight amino acid sequences, identified from 12S oat globulin (GDVVALPA and DVVALPAG), and other sequences rich in amino acids like proline, leucine, valine, phenylalanine, and glutamine. The results suggest that proline and hydrophobic amino acids may favor hydrophobic interactions and hydrogen bonding with the target enzymes, especially the Leu-Pro sequence found in potent DPP-IV inhibitors.

This study investigated the inhibitory effects of the Ethanol Extract (EE), Free Phenolic (TF), Esterified Phenolic (TE) and Insoluble-bound Phenolic (TI) from Rhus chinensis Mill. fruits on α-glucosidase, Dipeptidyl Peptidase-4 (DPP-IV), and the formation of Advanced Glycation End (AGE) products. Results showed that the TF had the strongest inhibition against α-glucosidase and DPP-IV with IC50 of 0.56 ± 0.04 and 66.08 ± 1.36 μg/mL, respectively (p < 0.05). TI exhibited the strongest inhibitory effect on the formation of AGEs with IC50 of 0.43 ± 0.03 mg/mL (p < 0.05). Two major compounds (myricetin-3-O-rhamnoside and quercetin-3-O-rhamnoside) showed additive or synergistic effects on α-glucosidase inhibition, while displayed antagonistic effect on DPP-IV inhibition. Correlation analysis indicated that myricetin-3-O-(6″-galloyl) glycoside and myricetin O-gallate contributed significantly on α-glucosidase inhibition, while di-O-galloyl-glucoside and its isomer may contribute remarkably toward DPP-IV inhibition. Protocatechuic acid and myricetin-3-O-rhamnoside showed a positive correlation with the suppression of AGEs formation. Those results may provide some scientific information for exploring R. chinensis fruits as nutraceuticals and/or functional foods to prevent or improve diabetes.

Phyllanthus niruri Linn. (Euphorbiaceae) is a small herb and is categorised as one of the rich medicinal plants throughout the world. This study aimed to evaluate the P. niruri L. whole plant extract (PNE) for secondary metabolite assay (total phenolic and terpenoid content) followed by the potential antioxidant activity (ABTS diammonium salt radical assay, DPPH · activity, superoxide anion (O 2 - ) radicals' assay, and nitric oxide (NO) radical generation) and antidiabetic activity in vivo and in vitro in streptozotocin (STZ) induced albino mice. PNE showed good scavenging activity with a value of 286.45 ± 6.55 mg TE/g and 194.54 ± 4.64 mg TE/g in ABTS and DPPH assays respectively. In the superoxide anion assay, the PNE caused a dose-dependent inhibition at the lowest IC 25 value of 0.17 ± 0.00 mg/mL compared to ascorbic acid (IC 25 of 0.25 ± 0.02 mg/mL). The scavenging ability of PNE against nitric oxide showed an IC 25 of 1.13 ± 0.04 mg/mL compared to ascorbic acid (IC 25 4.78 ± 0.09 mg/mL). Unlike diabetic control mice, the PNE-treated diabetic mice presented significant amelioration of glycaemia and lipid dysmetabolism. Phytochemicals like Astragalin, Gallocatechin, Ellagic acid, Gallic acid, Brevifolin carboxylic acid, Phyllnirurin, and Hypophyllanthin showed significant docking score (> -4) of inhibitory potential with DPP-IV protein. Results indicated that PNE phytochemicals could be a promising antidiabetic agent by targeting DPP-IV.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease that requires multiple therapeutic strategies for its management. Bioactive peptides with multiple anti-diabetic targets are attractive therapeutic molecules. The present study was conducted to identify additional anti-diabetic targets of α-glucosidase inhibitory peptides, SVPA, SEPA, STYV, and STY. The α-glucosidase inhibitory activity of the peptides was in the order STYV > STY > SEPA > SVPA while molecular docking against human dipeptidyl peptidase IV (DPP-IV) showed that SVPA had the best binding affinity. In contrast, in vitro studies indicated that SEPA had a significantly higher (P < 0.05) DPP-IV inhibitory activity (IC50 = 5.78 ± 0.19 mM) than other peptides. SVPA and SEPA showed mixed inhibition pattern while STYV and STY were uncompetitive inhibitors of the enzyme. IPI (diprotin A), STYV and STY were not cytotoxic while SEPA displayed some cytotoxicity. In differentiated 3T3-L1 adipocytes, SVPA and STYV were found to induce a significant (P < 0.05) decrease in intracytoplasmic lipid accumulation when added during the differentiation process while STY, GSH and IPI caused significant reduction (P < 0.05) in the lipid accumulation when added after the differentiation. The SVPA, SEPA and STYV were better scavengers of methylglyoxal than STY but STYV had the best scavenging activities toward reactive oxygen species and nitric oxide. It was concluded that the four α-glucosidase inhibitory peptides including IPI have multiple targets against type T2DM but, overall, of the four peptides evaluated, STYV tends to have better potential for application as a multifunctional anti-diabetic peptide. [ABSTRACT FROM AUTHOR]

• Acacia leucophloea (AL) exhibits promising multi-targeted anti-diabetic efficacy. • AL fractions rich in phenols/flavonoids excel in antioxidant/diabetic potential. • Five out of six compounds reported for the first time in AL active fractions. • Apigenin-7-O-glucoside and isoquercitrin exhibit enhanced 2-NBDG uptake in L6 myotubes. Acacia leucophloea (AL) has been used traditionally to treat diabetes, cancer, inflammation, ophthalmia, haemorrhoids and leukoderma, however the scientific evidence validating its antidiabetic activity is limited. Employing a multi-targeted therapeutic strategy could be advantageous for the management of type 2 diabetes mellitus which is strongly correlated with oxidative stress-induced pathways. The present study was intended to evaluate the antidiabetic and antioxidant potential of AL via in vitro assays, validating its traditional medicinal significance. Anti-diabetic potential of the AL extract, its fractions and isolated compounds was assessed through the determination of α-glucosidase, DPP-IV inhibition, anti-glycation activity, and glucose uptake using 2-NBDG in differentiated L6 myoblast, along with cytotoxicity studies. Total phenolic and flavonoid content was measured and the antioxidant potential was evaluated using in vitro assays i.e. , DPPH, ABTS and FRAP. In addition, quantitative determination of isolated compounds and their purity was analysed using HPLC-DAD. Fractions with the highest phenolic/flavonoid content (VI to XIII of AL) demonstrated substantial antioxidant and antidiabetic potential across selected therapeutic targets and these active fractions yielded six compounds upon fractionation using column chromatographic techniques. Structures of these compounds were examined using spectroscopic techniques and were identified as isoquercitrin, quercitrin, luteolin, epigallocatechin-3-O-(3 ″ -O-methyl)-gallate, apigenin-7-O-glucoside and ethyl gallate. Isolated compounds showed significant DPP-IV inhibitory activity in a concentration-dependent manner with the highest activity with minimum IC 50 being possessed by isoquercitrin (IC 50 4.28 ± 0.32 µ M). At a concentration of 200 µ M, apigenin-7-O-glucoside displayed a considerable glycation inhibitory effect (81.57 ± 2.66 %), surpassing the effect of other compounds. Moreover, at a concentration of 50 μM, the compounds apigenin-7-O-glucoside and isoquercitrin have increased the glucose uptake in L6 myotubes by 11.5 % and 11 % respectively, compared to a 6.1 % increase by the standard drug metformin. Notably, this study reveals for the first time the potential of both apigenin-7-O-glucoside and isoquercitrin to enhance glucose uptake in L6 myotubes. AL and its isolated compounds exhibit promising effects in ameliorating post-prandial hyperglycemia. Their multifaceted therapeutic potential prompts further investigation to elucidate the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

DPP-IV inhibitors have been immersed as promising pathway to treat Type 2 diabetes. Here we have reported designing of coumarin derivatives as DPP-IV inhibitors. Designed compounds have been studied for their binding with DPP-IV enzyme through molecular docking followed by synthesis. All synthesized compounds have been fully characterized and screened for DPP-IV inhibition activity. Two compounds showed very good inhibition at 10 μM concentration. [ABSTRACT FROM AUTHOR]

Calanus finmarchicus is a crustacean currently used as a source of marine lipid. The lipids are extracted by enzymatic protein hydrolysis, while the remaining peptide fraction is regarded as a byproduct. In the present work, ten different commercial proteases and endogenous C. finmarchicus proteases were used to produce a set of 63 protein hydrolysates. Protease concentration and hydrolysis time were varied. Hydrolysates were characterized using size-exclusion chromatography and 1H nuclear magnetic resonance spectroscopy. Addition of commercial proteases had unremarkable effect on the yield and molecular weight distribution. This was attributed to the strong impact of endogenous enzymes dominating the hydrolysis process. However, multivariate classification based on 1H NMR spectra revealed subtle variations in composition of hydrolysates produced using different enzymes. The hydrolysates were further evaluated for DPP-IV inhibition and antioxidant activity. The hydrolysates showed significantly higher bioactivity than the unhydrolyzed control. A representative hydrolysate (CaFi55) was fractionated using semipreparative size-exclusion chromatography. A fraction consisting of short peptides with an average chain length of five amino acids (F2) , was identified as a major contributor to the DPP-IV inhibitory activity (IC 50 = 0.70 ± 0.07 mg/mL). [Display omitted] • A total of 63 Calanus finmarchicus hydrolysates were produced and characterized. • SEC and NMR revealed characteristic short peptides and known marine metabolites. • Hydrolysates inhibited DPP-IV enzyme (36–72%) and showed good antioxidant activity. • Low molecular weight fraction inhibited DPP-IV with IC 50 of 0.70 ± 0.07 mg/mL. • Endogenous enzymes were efficient in hydrolysis and yielding bioactive peptides. [ABSTRACT FROM AUTHOR]

Lactobacillus strains were screened for inhibition of dipeptidyl peptidase IV (DPP-IV) and α-glucosidase. Cell-free excretory supernatants (CFS) and cell-free extracts (CFE) of 21 strains were prepared, and most of them showed DPP-IV inhibition in a concentration-dependent manner, which started at the exponential phase and peaked at the stationary phase of the Lactobacillus. The CFS bioactivity was heat-resistant, stable to acid–alkali and glucosidase treatment. Trypsin treatment specifically elevated CFS's DPP-IV inhibition. Lactobacillus plantarum strains CFS displayed different protein patterns and trypsin sensitive bands on SDS-PAGE, demonstrating specific peptide-cleavage contributes to higher inhibition. Seven strains with highest DPP-IV inhibition also displayed α-glucosidase inhibitory activity, of which, three strains of L. plantarum and one of Lactobacillus brevis showed tolerance to simulated gastrointestinal tract conditions and high HT-29 cell adhesion. This initial report of lactobacilli secreting strong DPP-IV and α-glucosidase inhibition components will be beneficial for selection and application of anti-diabetic probiotics.

Herein, we have designed various benzisoxazole acetamide derivatives with and without glycine spacer as DPP-IV inhibitors. Compounds 9a-d and 11a-e were synthesized and screened for their in vitro DPP-IV inhibition. Compounds 11a and 11c showed moderate activity for DPP-IV inhibition, whereas other remained inactive at 25-200 µM concentrations. DPP-IV inhibition can be a good strategy for modulating diabetes and cancer; hence, we have screened compounds 9a-d and 11a-e for their anticancer activity using MTT assay against A549 and MCF7 cell lines. Compounds 9a-d without glycine spacer have shown good anticancer activity compared to compounds 11a-e with glycine spacer. Compound 9b has shown moderate activity with IC50 values 4.72 ± 0.72 and 4.39 ± 0.809 µM against A549 and MCF7 cell lines, respectively. Interestingly, compound 9c with cyano group has shown very good anticancer activity with IC50 2.36 ± 0.34 µM against MCF7 cell line as compared to fluorouracil with IC50 45.04 ± 1.02 µM. [ABSTRACT FROM AUTHOR]

Food-derived bioactive peptides have gained attention for their role in preventing chronic diseases. Edible insects are viable sources of bioactive peptides owing to their high protein content and sustainable production. In this study, whole crickets ( Gryllodes sigillatus) were alcalase-hydrolyzed to a degree of hydrolysis (DH) ranging from 15 to 85%. Antioxidant activity, angiotensin converting enzyme (ACE), and dipeptidyl peptidase-4 (DPP-IV)- inhibition of the cricket protein hydrolysates (CPH) were evaluated before and after simulated gastrointestinal digestion (SGD). Antioxidant activity was similar among CPH, whereas ACE and DPP-IV inhibition was greater (p < 0.05) in CPH with 60–85% DH. Bioactivity improved after SGD. CPH allergenicity was evaluated using human shrimp-allergic sera. All sera positively reacted to tropomyosin in the unhydrolyzed cricket and CPH with 15–50% DH, whereas 60–85% DH showed no reactivity. In conclusion, CPH (60–85% DH) had the greatest bioactive potential and lowest reactivity to tropomyosin, compared with other CPH and the unhydrolyzed control. [ABSTRACT FROM AUTHOR]

DPP-IV “a moonlighting protein” has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC 50 value 24 ± 0.1 nM against A549 cell line. [ABSTRACT FROM AUTHOR]

We investigated the effect of sequential treatment escalation with dapagliflozin and saxagliptin on beta cell function in patients with T2DM insufficiently controlled on metformin monotherapy during a hyperglycaemic clamp investigation. Twenty-six patients (19 males, age 63.5 ± 7.0 years; duration of diabetes 8.8 ± 4.7 years; HbA1c 63.9 ± 15.8 mmol/mol; mean ± SD) were enrolled in the study. During a first treatment period (TP1) all patients received 10 mg dapagliflozin for one month, followed by the addition of 5 mg saxagliptin or placebo for another month (TP2). At baseline and at the end of each treatment period, fasting glucose and insulin levels were analysed, and a hyperglycaemic clamp with the measurement of plasma C-peptide, insulin, proinsulin, and glucagon was performed. Treatment with dapagliflozin reduced fasting glucose levels and insulin resistance (TP1). Within the hyperglycaemic clamp, C-peptide and insulin concentrations increased after the addition of dapagliflozin in TP1 (0.48 ± 0.45 nmol * h/l; 6.24 ± 17.9 mU * h/l) and further improved after the addition of saxagliptin in TP2 (0.38 ± 0.34 nmol * h/l; 6.59 ± 10.15 mU * h/l). Acute insulin response did not change after the addition of dapagliflozin (TP1), but significantly improved af ter the addit ion of saxagliptin in TP2 (0.89 ± 0.76 mU * h/l). Both drugs improved the C-peptide/proinsulin ratio. After the addition of saxagliptin, the glucagon/insulin ratio significantly declined (TP2). Treatment escalation with dapagliflozin and saxagliptin exhibit additive effects on beta cell capacity, and improves alpha and beta cell integrity. [ABSTRACT FROM AUTHOR]

β-Lactoglobulin hydrolysates (βlgHs) were generated using elastase at enzyme-to-substrate ratios (E:S) of 0.5, 1.0 and 1.5% in order to reach target degree of hydrolysis (DH) values of 9 and 13%. The impact of different E:S during manufacture on hydrolysates having similar DHs was assessed. Samples with similar DHs generated with different E:S showed comparable molecular mass distribution profiles and in vitro dipeptidyl peptidase IV (DPP-IV) inhibitory activities ( p > 0.05). Liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis showed that 62 and 84% of the peptides identified were common within hydrolysates having a similar DH of 9 or 13%, respectively. Differences in the peptides identified within hydrolysates having similar DHs may be due to E:S dependent modifications in specificity and enzyme kinetics. Overall, this study showed that reduction in E:S while targeting the development of a similar DH for βlgHs may be employed to reduce the cost of hydrolysate production without having an adverse impact on the bioactivity and physicochemical properties studied herein. [ABSTRACT FROM AUTHOR]

BACKGROUND Diabetes and hypertension are diseases affecting a high proportion of the world population; the use of food-based products such as common bean peptides may contribute to reduce the risk of complications associated to chronic diseases. The aim was to produce and characterize peptides from common bean protein isolates and evaluate their potential to inhibit markers of type-2 diabetes, hypertension and oxidative stress. RESULTS Mexican black and Brazilian Carioca bean isolated proteins were characterized after pepsin/pancreatin digestion. Also, four synthesized pure peptides, originally found in these beans, were evaluated. Bean protein digests and pure peptides exerted dipeptidyl peptidase- IV ( DPP-IV) inhibition ( IC50 = 0.03-0.87 mg dry weight ( DW) mL−1). Lineweaver-Burk plots and computational modeling showed competitive inhibition of DPP-IV. Angiotensin-converting enzyme ( ACE) inhibition ranged from IC50 = 0.09 to 0.99 mg DW mL−1, and α-glucosidase inhibition ranged from 36.3 to 50.1% mg−1 DW. Carioca Perola bean digested proteins presented the highest antioxidant capacity (269.3 mmol L−1 Trolox equivalent g−1 DW) as the peptide KTYGL ( P > 0.05) with the most potent DPP-IV and ACE inhibition. CONCLUSION Peptides from common bean have antidiabetic and antihypertensive potential regardless of their antioxidant capacity. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Dietary proteins have recently been investigated as a new source of DPP-IV inhibitory peptides with limited side effects and promising applications. Numerous studies have highlighted and identified peptide sequences able to inhibit DPP-IV activity in vitro , mostly from milk proteins. However, the correlation to in vivo studies remains scarce because standard in vitro assays with purified enzyme do not accurately simulate key factors impacting peptide bioactivity such as intestinal and brush border enzymes or cellular permeability. Therefore, a DPP-IV activity inhibition assay is here proposed using non differentiated confluent Caco-2 cells to rapidly assess food-derived peptide inhibitory potential in approaching intestinal conditions. DPP-IV gene expression was first checked and specific DPP-IV substrate was used to implement the assay. Using a specific DPP-IV inhibitor confirmed that non differentiated Caco-2 cells express measurable DPPIV activity. This in situ assay was then applied to digests which already demonstrated a DPP-IV inhibitory potential with a standard assay using purified enzyme. Bovine hemoglobin and cuttlefish hydrolysate digests from simulated gastrointestinal digestion exerted a dose response inhibition on DPP-IV activity but displayed different inhibitory potentials. [ABSTRACT FROM AUTHOR]

The in vitro dipeptidyl peptidase- IV ( DPP- IV) inhibitory activity of a Brewers' spent grain protein-enriched isolate ( BSG- PI) Alcalase™ hydrolysate (AlcH), which had previously been identified as a relatively potent angiotensin-converting enzyme ( ACE) inhibitor, was determined. The half maximal DPP- IV inhibitory concentration ( IC50) value of AlcH following 240-min digestion was 3.57 ± 0.19 mg mL−1. Ultrafiltration fractionation did not significantly increase the DPP- IV inhibitory activity of the AlcH fractions. Subjection of AlcH to simulated gastrointestinal digestion ( SGID), which yielded SAlcH, resulted in a significant increase in DPP- IV inhibitory activity ( P < 0.05), particularly after the intestinal phase of digestion. Following semi-preparative reverse phase high performance liquid chromatography ( RP- HPLC) fractionation of SAlcH, fraction 28 was identified as having highest mean DPP- IV inhibitory activity. Two novel DPP- IV inhibitory peptides, ILDL and ILLPGAQDGL, with IC50 values of 1121.1 and 145.5 μ m, respectively, were identified within fraction 28 of SAlcH following ultra-performance liquid chromatography ( UPLC)-tandem mass spectrometry ( MS/ MS). BSG protein-derived peptides were confirmed as having dual ACE and DPP- IV inhibitory activities. [ABSTRACT FROM AUTHOR]

[Display omitted] • Denaturation of milk protein concentrate-85 (MPC85) did not change PDCAAS value. • The peptide profile of MPC85 changed with whey protein (WP) denaturation level. • Low denatured MPC85 had higher digestibility and bioactivity upon gastric digestion. • Subjection of MPC85 to gastrointestinal digestion released many peptides <1 kDa. The impact of whey protein (WP) denaturation on the in vitro digestibility and biological activity of milk protein concentrate-85 (MPC85) was investigated. MPC85S1 and MPC85S2 having undenatured WP levels equal to 16.6 and 6.0 g/100 g overall protein, respectively, had similar in vitro protein digestibility corrected amino acid scores equal to 1.14. The samples were subjected to in vitro simulated gastrointestinal digestion while sampling was performed every 30 min during gastric (GD) followed by intestinal (GID) digestion. Liquid chromatography–mass spectroscopy showed that MPC85S1-GD, MPC85S2-GD, MPC85S1-GID and MPC85S2-GID had 50, 38, 47 and 66 unique peptides, respectively. The degree of hydrolysis, molecular mass distribution, dipeptidyl peptidase-IV inhibition, oxygen radical absorbance capacity and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity of the digests were compared. Overall, the results showed higher digestibility and bioactivities for low-denatured MPC85 compared to high-denatured MPC85 upon GD, however, following GID, both samples were digested to a similar extent. [ABSTRACT FROM AUTHOR]

[Display omitted] GPR55 has been recognized as a novel anti-diabetic target exerting positive effects on beta cell function and mass. This study evaluated the metabolic actions and therapeutic efficacy of GPR55 agonist abnormal cannabidiol (Abn-CBD) administered alone and in combination with sitagliptin in diet-induced obese-diabetic mice. Chronic effects of 21-day oral administration of Abn-CBD (0.1 µmol/kg BW) monotherapy and in combination with sitagliptin (50 mg/kg BW) were assessed in obese-diabetic HFF mice (n = 8). Assessments of plasma glucose, circulating insulin, DPP-IV activity, CRP, amylase, lipids, body weight and food intake were undertaken. Glucose tolerance, insulin sensitivity, DEXA scanning and islet morphology analysis were performed at 21-days. Sitagliptin, Abn-CBD alone and in combination with sitagliptin attenuated plasma glucose by 37–53 % (p < 0.01 – p < 0.001) and enhanced circulating insulin concentrations by 23–31 % (p < 0.001). Abn-CBD alone and with sitagliptin reduced bodyweight by 9–10 % (p < 0.05). After 21-days, Abn-CBD in combination with sitagliptin (44 %; p < 0.01) improved glucose tolerance, whilst enhancing insulin sensitivity by 79 % (p < 0.01). Abn-CBD increased islet area (86 %; p < 0.05), beta cell mass (p < 0.05) and beta cell proliferation (164 %; p < 0.001), whilst in combination with sitagliptin islet area was decreased (50 %; p < 0.01). Abn-CBD alone, in combination with sitagliptin or sitagliptin alone decreased triglycerides by 34–65 % (p < 0.001) and total cholesterol concentrations by 15–25 % (p < 0.001). In addition, Abn-CBD in combination with sitagliptin reduced fat mass by 19 % (p < 0.05) and reduced CRP concentrations (39 %; p < 0.05). These findings advocate Abn-CBD monotherapy and in combination with sitagliptin as a novel and effective approach for bodyweight control and the treatment of glucose intolerance and dyslipidaemia in type-2-diabetes. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-IV (DPP-IV) is an exopeptidase mainly present in epithelial tissues of the liver, kidney, and intestine. It is involved in the cleavage of a variety of substrates including the incretin hormones like glucagon-like peptide-1 (GLP-1). GLP-1 binds to the GLP-1 receptors of pancreatic β-cells and leads to β-cell proliferation and increases insulin secretion through associated gene expression. In diabetes, a constant increase in the glucose level leads to glucotoxicity, which destroys pancreatic β-cells, decreases the insulin level, and further increases the blood glucose level. Inhibition of DPP-IV is one of the strategies for the treatment of type 2 diabetes. In recent years, peptides derived from a variety of dietary proteins have been reported to exhibit inhibitory activity against the DPP-IV enzyme. Such peptides should also be protected from the action of digestive enzymes to keep their bioactivity intact. Therefore, the present investigation was aimed to evaluate the in vitro DPP-IV inhibition potential and in vivo antidiabetic potential of α-lactalbumin in non-encapsulated hydrolysate (NEH), freeze-dried encapsulated hydrolysate (FDEH), and emulsified encapsulated hydrolysate (EEH) forms. Percent DPP-IV inhibition by the NEH, FDEH, and EEH after simulated gastrointestinal digestion was 36 ± 2.28, 54 ± 2.02, and 64 ± 2.02, respectively. The oral administration of the NEH, FDEH, and EEH at a dose of 300 mg/kg body weight was evaluated in nicotinamide-streptozotocin-induced type 2 diabetic experimental rats in a study of 30 days. Rats in the diabetic control group showed an increase in the blood glucose level and liver function enzymes and a decrease in GLP-1, insulin, and antioxidative enzymes. Administration of hydrolysates reversed the parameters by lowering the blood glucose level and increasing GLP-1 and insulin levels in plasma. The blood lipid profile, liver enzyme (ALT, AST, and AP) levels, and catalase and superoxide dismutase activity were also found to be normalized and better managed in experimental diabetic rats.

Enzymatic hydrolysis of whey protein (WP) was carried out under pH-controlled and non pH-controlled conditions using papain and a microbial-derived alternative (papain-like activity). The impact of such conditions on physicochemical and bioactive properties was assessed. WP hydrolysates (WPH) generated with the same enzyme displayed similar degree of hydrolysis. However, their reverse-phase liquid chromatograph mass spectrometry peptide profiles differed. A significantly higher oxygen radical absorbance capacity (ORAC) value was obtained for WP hydrolysed with papain at constant pH of 7.0 compared to the associated WPH generated without pH regulation. In contrast, there was no significant effect of pH regulation on dipeptidyl peptidase IV (DPP-IV) properties. WP hydrolysed with papain-like activity under pH regulation at 7.0 displayed higher ORAC activity and DPP-IV inhibitory properties compared to the associated WPH generated without pH regulation. This study has demonstrated that pH conditions during WPH generation may impact on peptide release and therefore on WPH bioactive properties. [ABSTRACT FROM AUTHOR]

The incretin hormones are extremely rapidly metabolized by the ubiquitous enzyme dipeptidyl peptidase IV (DPP-IV). Therefore, DPP-IV inhibitors which can prolong the incretin effect are the newest and promising drugs for management of type 2 diabetes. In this study, we investigated whether Bifidobacteria colonizing the human gut possess DPP-IV inhibitory activity. Cell-free intracellular extracts of 13 Bifidobacterium strains isolated from breast-fed infant faecal samples were prepared and screened for DPP-IV inhibitory activity, and two Bifidobacterium strains- Bif. longum BBMN68 and Bif. lactis Bb12-were used as reference strains. Most of the strains showed varying levels of DPP-IV inhibitory property (7-27%). Strains of Bifidobacterium adolescentis IF1-11 and Bifidobacterium bifidum IF3-211 showed the greatest DPP-IV inhibitory activity (27 and 25%) as well as good in vitro probiotic properties. This initial finding suggested that new beneficial function of Bifidobacteria is strain-dependent and the strains or their components may have the potential application for management of type 2 diabetes via inhibiting gastrointestinal DPP-IV activity. Further investigations into the isolation and identification of the bioactive components of Bifidobacteria are warranted. Significance and Impact of the Study Our results show that Bifidobacteria isolated from breast-fed infants' faecal samples possess DPP-IV inhibitory activity. Strains of Bifidobacterium bifidum IF3-211 and Bifidobacterium adolescentis IF1-11, which showed excellent DPP-IV inhibitory properties as well as good in vitro probiotic properties, are expected to be beneficial for application as anti-diabetic probiotics. [ABSTRACT FROM AUTHOR]

Lactobacillus strains were screened for inhibition of dipeptidyl peptidase IV (DPP-IV) and α-glucosidase. Cell-free excretory supernatants (CFS) and cell-free extracts (CFE) of 21 strains were prepared, and most of them showed DPP-IV inhibition in a concentration-dependent manner, which started at the exponential phase and peaked at the stationary phase of the Lactobacillus . The CFS bioactivity was heat-resistant, stable to acid–alkali and glucosidase treatment. Trypsin treatment specifically elevated CFS's DPP-IV inhibition. Lactobacillus plantarum strains CFS displayed different protein patterns and trypsin sensitive bands on SDS-PAGE, demonstrating specific peptide-cleavage contributes to higher inhibition. Seven strains with highest DPP-IV inhibition also displayed α-glucosidase inhibitory activity, of which, three strains of L.   plantarum and one of Lactobacillus brevis showed tolerance to simulated gastrointestinal tract conditions and high HT-29 cell adhesion. This initial report of lactobacilli secreting strong DPP-IV and α-glucosidase inhibition components will be beneficial for selection and application of anti-diabetic probiotics. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effect of enzymatic hydrolysis conditions (enzyme types and hydrolysis time) of date seed protein hydrolysates (DSPH) on in-vitro inhibition of molecular markers related with diabetic and hypercholesteremia. The DSPH was prepared using alcalase, bromelain, papain, and protease at different hydrolysis time (HT) (2, 4 and 6 h). Higher degree of hydrolysis was observed for papain at 6 h HT. The results showed that alcalase and bromelain generated DSPHs at 6 h HT greatly improved the pancreatic lipase inhibition activity while the cholesterol esterase inhibition activity was greatly enhanced with alcalase and protease at 6 h HT and papain generated DSPHs at 4 h HT. Bromelain generated DSPH displayed the highest inhibition of dipeptidyl peptidase-IV (DPP-IV) and amylase at 6 and 2 h hydrolysis time, respectively. All the enzymes at 2 h HT except that of papain showed the highest α-glucosidase inhibitory activities. These results revealed that the DSPH displayed enhanced inhibitory activities towards molecular markers related with diabetes and obesity and thus have promising potential to be used as health-promoting ingredients in the fabrication of functional foods. [Display omitted] • Date seed protein hydrolysates (DSPHs) were produced using four different enzymes. • DSPHs were evaluated for in-vitro anti-diabetic and anti-hypercholesteremia effect. • Alcalase and bromelain 6h DSPHs improved pancreatic lipase inhibitory activity. • Bromelain-6h generated DSPHs displayed the highest inhibition of DPP-IV. • All the 2h-DSPHs except papain showed highest α-glucosidase inhibitory activities. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the effect of bioactive peptide fractions from de-hulled hard-to-cook (HTC) bean on enzyme targets of type-2 diabetes and oxidative stress. Protein isolates from Pinto Durango and Negro 8025 beans were hydrolyzed (120 min) with either alcalase® or bromelain and separated into five peptide fractions (< 1, 1–3.5, 3.5–5, 5–10, and > 10 kDa) using an ultrafiltration membrane system. The < 1 kDa pinto Durango-bromelain fraction showed the best inhibition of α-amylase (49.9 ± 1.4%), and the < 1 kDa pinto Durango-alcalase fraction inhibited both, α-glucosidase (76.4 ± 0.5%), and dipeptidyl peptidase-IV (DPP-IV, 55.3 ± 1.6%). Peptides LLSL, QQEG and NEGEAH were present in the most potent fractions. Hydrolysates and peptide fractions showed antioxidant capacity (ORAC: 159.6 ± 2.9 to 932.6 ± 1.1 mmol TE/g) and nitric oxide inhibition (57.5 ± 0.9 to 68.3 ± 4.2%). Hydrolysates and fractions < 1 and 1–3 kDa were able to increase glucose-stimulated insulin secretion from iNS-1E cells up to 57% compared to glucose control. Hydrolysates from HTC beans inhibited enzymes related to diabetes management, being the smallest peptides (< 1 kDa) the most potent. HTC bean could be a source of protein to produce bioactive peptides with potential antidiabetic properties. [ABSTRACT FROM AUTHOR]

Purpose: Although recent reports suggest an association between saxagliptin and an increased risk of admissions for heart failure, it is not clear whether dipeptidyl peptidase IV (DPP-IV) inhibition contributes to heart failure in high-risk patients. The purpose of this research is to understand heart failure risk among high-risk patients with type 2 diabetes. Methods: This is a systematic review of data published in full papers and abstract form using the terms DPP-IV inhibitors and heart failure published since October 2013. Data from insurance and hospital databases were combined with those from multiple published trials, including the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial; Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care (EXAMINE), and Vildagliptin in Ventricular Dysfunction Diabetes (VIVIDD) trial as well as pooled analyses of linagliptin and saxagliptin placebo-controlled trials to examine heart failure among patients represented in those datasets. Findings: A meta-analysis of the 9 datasets showed an increase in heart failure with dipeptidyl peptidase IV inhibitors of 15% (P = 0.017). There was no statistical heterogeneity, nor was there a statistical difference between cohort studies and randomized, controlled trials (P = 0.3), even though cohort studies alone were not significant (relative risk: 1.1; P = 0.32). Removing SAVOR-TIMI 53 data produced an insignificant increase in heart failure of 12% (P = 0.09) in the rest of the studies. In the randomized, controlled trials, the increased risk was 24% (P = 0.002). There was no statistical difference between those studies with and without baseline cardiovascular disease (P = 0.58), although the cardiovascular disease studies were borderline significant (P = 0.06). There was no publication bias. Implications: There are data from studies using sitagliptin, saxagliptin, and alogliptin showing that these agents may increase the risk of hospitalization for heart failure. More data are required for a definitive conclusion. [ABSTRACT FROM AUTHOR]

Abstract: A series of 19 heterocyclic homoprostanoids were synthesized from easily available oleic and ricinoleic acids and evaluated for their possible antioxidant, anti-inflammatory and anti-hyperlipidaemic activities. Compounds with thioxo- and oxoimidazole ring (1) and (2) have shown potent antioxidant activity with IC50 values 0.23±0.09 and 0.41±0.01mM comparable with standard ascorbic acid. Compound (3) with a quinoxaline ring showed maximum inhibition of BSA denaturation at 1mM concentration and comparable with standard diclofenac. Incorporation of electron withdrawing substitutions like chloro- and nitro-groups in the quinoxaline ring has resulted in an increase anti-inflammatory activity. Test compounds (3), (3a) and (3c) showed modest inhibition of DPP-IV in vitro. However, the unsubstituted quinoxaline (3) and substituted quinoxalines (3b and 3c) reduced plasma glucose levels indicating the presence of hypoglycemic activity. [ABSTRACT FROM AUTHOR]

A number of functional foods containing seaweed-derived peptides are currently commercialized. Some seaweed derived peptide-containing products include Wakame peptide® and Nori peptide S®. To develop functional foods with the addition of Ulva spp. peptides, the isolation and identification of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from hydrolysates of this seaweed was performed. Ulva spp. peptides were fractionated and purified sequentially by anion exchange, ultrafiltration, and reversed phase high performance liquid chromatography. The fractions obtained from each analytical step were collected and the in vitro enzyme inhibitory activity was evaluated. The applied purification process increased the in vitro DPP-IV inhibitory activity. The inhibition mechanism of DPP-IV of the most active fraction was evaluated and it was analyzed by MALDI-TOF. A peptide SLAVSVH was identified. It has 57% of hydrophobic residues in their sequence (including Ala and branched chain amino acids), which could be a common feature among inhibitory peptides of DPP-IV. Molecular docking analysis showed that SLAVSVH/DPP-IV complex was stabilized by CH–π interactions between the side chains of Val6 with the indol of Trp629, and between rings of His7 with Trp563. The energy values obtained for the peptide under study indicate that it is a good candidate to inhibit DPP-IV. • Two protease combinations were used to obtain hydrolysates from edible algae Ulva spp. • The isolation and identification of DPP-IV inhibitory peptides was performed. • The applied purification process increased the in vitro DPP-IV inhibitory activity. • A novel DPP-IV inhibitory peptide was identified by MALDI-TOF (SLAVSVH). • Molecular docking analysis showed that SLAVSVH is a good inhibitor of DPP-IV. [ABSTRACT FROM AUTHOR]