RESUMEN

The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with -7.83 and - 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos , Digestión , Glútenes , Péptidos , Peptidil-Dipeptidasa A , Ratas Endogámicas SHR , Zea mays , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Antihipertensivos/química , Antihipertensivos/farmacología , Animales , Glútenes/química , Glútenes/metabolismo , Humanos , Zea mays/química , Zea mays/metabolismo , Ratas , Células CACO-2 , Péptidos/química , Péptidos/farmacología , Masculino , Digestión/efectos de los fármacos , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Presión Sanguínea/efectos de los fármacos , Hipertensión/metabolismo , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Tracto Gastrointestinal/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Hidrólisis

RESUMEN

The objective of this study was to investigate the nutrient composition of low-grade New Zealand commercial fish (Gemfish and Hoki) roe and to investigate the effects of delipidation and freeze-drying processes on roe hydrolysis and antioxidant activities of their protein hydrolysates. Enzymatic hydrolysis of the Hoki and Gemfish roe homogenates was carried out using three commercial proteases: Alcalase, bacterial protease HT, and fungal protease FP-II. The protein and lipid contents of Gemfish and Hoki roes were 23.8% and 7.6%; and 17.9% and 10.1%, respectively. The lipid fraction consisted mainly of monounsaturated fatty acid (MUFA) in both Gemfish roe (41.5%) and Hoki roe (40.2%), and docosahexaenoic (DHA) was the dominant polyunsaturated fatty acid (PUFA) in Gemfish roe (21.4%) and Hoki roe (18.6%). Phosphatidylcholine was the main phospholipid in Gemfish roe (34.6%) and Hoki roe (28.7%). Alcalase achieved the most extensive hydrolysis, and its hydrolysate displayed the highest 2,2-dipheny1-1-picrylhydrazyl (DPPH)˙ and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities and ferric reducing antioxidant power (FRAP). The combination of defatting and freeze-drying treatments reduced DPPH˙ scavenging activity (by 38%), ABTS˙ scavenging activity (by 40%) and ferric (Fe3+) reducing power by18% (p < 0.05). These findings indicate that pre-processing treatments of delipidation and freeze-drying could negatively impact the effectiveness of enzymatic hydrolysis in extracting valuable compounds from low grade roe.

Asunto(s)

Antioxidantes , Hidrolisados de Proteína , Animales , Antioxidantes/farmacología , Antioxidantes/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Nueva Zelanda , Liofilización , Hidrólisis , Peces/metabolismo , Péptido Hidrolasas/metabolismo , Péptido Hidrolasas/química , Productos Pesqueros/análisis , Subtilisinas

RESUMEN

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 µg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.

Asunto(s)

Antivirales , Virus del Dengue , Microalgas , Virus del Dengue/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Animales , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Dengue/tratamiento farmacológico , Dengue/virología , Péptidos/farmacología , Péptidos/química , Serogrupo , Chlorocebus aethiops , Humanos , Aedes/efectos de los fármacos , Células Vero

RESUMEN

Angiotensin I-converting enzyme (ACE) regulates blood pressure through the renin-angiotensin system. Douchi, a traditional fermented soybean condiment, may have antihypertensive effects, but research on ACE inhibitory peptides from Douchi hydrolysates is limited. We hypothesized that enzymatic treatment could enhance ACE inhibitory peptide diversity and efficacy. We tested ten single enzymes and four combinations, finding pepsin-trypsin-chymotrypsin most effective. Hydrolysates were purified using Sephadex G-15 and reversed-phase HPLC, and peptides were identified via LC-MS/MS. Five peptides (LF, VVF, VGAW, GLFG, NGK) were identified, with VGAW as the most potent ACE inhibitor (IC50 46.6 ± 5.2 µM) showing excellent thermal and pH stability. Lineweaver-Burk plots confirmed competitive inhibition, and molecular docking revealed eight hydrogen bonds between VGAW and ACE. In hypertensive rats, VGAW significantly reduced blood pressure at 12.5, 25, and 50 mg/kg. These findings highlight Douchi as a source of ACE inhibitory peptides and suggest VGAW as a promising functional food ingredient.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos , Presión Sanguínea , Hipertensión , Péptidos , Peptidil-Dipeptidasa A , Ratas Endogámicas SHR , Animales , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Antihipertensivos/química , Antihipertensivos/farmacología , Ratas , Péptidos/química , Péptidos/farmacología , Péptidos/aislamiento & purificación , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/metabolismo , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Masculino , Presión Sanguínea/efectos de los fármacos , Simulación del Acoplamiento Molecular , Humanos , Glycine max/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Hidrólisis

RESUMEN

This study investigates the characterization, mechanisms of action, structure-activity relationships, and in vivo antihypertensive effects of ACE inhibitory peptides derived from sufu hydrolysate following simulated gastrointestinal digestion. Sufu was enzymatically digested using pepsin, trypsin, and chymotrypsin to mimic gastrointestinal conditions, followed by ultrafiltration to fractionate the peptides based on molecular weight. The fraction under 1 kDa exhibited the highest ACE inhibitory activity. LC-MS/MS analysis identified 119 peptide fragments, with bioinformatics screening highlighting 41 peptides with potential ACE inhibitory properties. Among these, two peptides, AWR and LLR, were selected and synthesized for in vitro validation, displaying IC50 values of 98.04 ± 2.56 µM and 94.01 ± 5.07 µM, respectively. Stability tests showed that both peptides maintained their ACE inhibitory activity across various temperatures and pH levels. Molecular docking and Highest Occupied Molecular Orbital analysis indicated strong binding interactions between these peptides and ACE, with the second-position tryptophan in AWR and the N-terminal leucine in LLR identified as key bioactive sites. These findings were further supported by molecular dynamics simulations, which confirmed the stability of the peptide-ACE complexes. In vivo studies using spontaneously hypertensive rats demonstrated significant reductions in both systolic and diastolic blood pressure, indicating that AWR and LLR have strong antihypertensive potential. This study illustrates that ultrafiltration, combined with LC-MS/MS and bioinformatics analysis, is an effective approach for the rapid screening of ACE inhibitory peptides. These results not only enhance our understanding of sufu-derived peptides but also offer promising implications for hypertension management.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos , Péptidos , Ratas Endogámicas SHR , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Antihipertensivos/farmacología , Antihipertensivos/química , Animales , Ratas , Péptidos/química , Péptidos/farmacología , Masculino , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Espectrometría de Masas en Tándem

RESUMEN

H. pylori is a highly pathogenic and prevalent pathogen that is a class I carcinogen. More than 50% of the world's population is infected with H. pylori. An anti-adhesive strategy is an effective way to antagonize H. pylori infection, which does not cause H. pylori resistance and is safer compared to antibiotic therapy. In the present study, to obtain rice bran protein-derived anti-adhesive activity peptides against H. pylori, an efficient enzymatic hydrolysis system was established, and it was found that rice bran protein hydrolysate prepared under specific conditions possessed anti-adhesive activity against H. pylori. The anti-adhesive activity of rice bran protein hydrolysate (RPH) was 43.74 ± 1.12% (4 mg mL-1), and gastric digestion (RPHA) had no significant effect on its activity. Hydrophobic amino acids and aromatic amino acids were important for its anti-adhesive activity. Further, 284 peptide sequences with potential anti-adhesive activity were isolated and identified from RPHA. Combined with molecular docking results, four novel anti-adhesive activity peptides were finally screened, namely LS5 (LSFRL), SN8 (SNTPGMVY), VV7 (VVNFGNL) and PV9 (PVLWGVPKG). Among them, PV9 showed the highest anti-adhesive activity of 59.64 ± 2.00% (4 mg mL-1). These four peptides could bind H. pylori adhesins BabA and SabA, occupying the binding sites of cell receptors and acting as anti-adhesion agents. In conclusion, four rice bran protein-derived anti-adhesive activity peptides against H. pylori can be used for the development of novel functional foods antagonizing H. pylori infection.

Asunto(s)

Adhesión Bacteriana , Helicobacter pylori , Oryza , Péptidos , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/fisiología , Oryza/microbiología , Oryza/química , Péptidos/farmacología , Péptidos/química , Adhesión Bacteriana/efectos de los fármacos , Simulación del Acoplamiento Molecular , Proteínas de Plantas/farmacología , Proteínas de Plantas/química , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química

RESUMEN

Egg white protein ovomucin and its hydrolysates were previously reported to exhibit anti-inflammatory and anti-adhesive activities. However, their potential to regulate pathogen colonization and disease severity has not been fully characterized. To investigate the effects of ovomucin (OVM) and its hydrolysates including ovomucin-Protex 26L (OP) and -pepsin/pancreatin (OPP) on host resistance to pathogen infection, a well-documented colitis model in mice for attaching and effacing E. coli pathogens, Citrobacter rodentium, was used in the current study. C57Bl/6J female mice were fed on a basal diet supplemented with OVM or its hydrolysates for 3 weeks prior to the C. rodentium challenge, with the dietary treatments continued for seven days. Body weight was not affected throughout the experimental period. OP supplementation resulted in lower (P < 0.05) pathogen loads at 7 dpi. Attenuated colitis severity was observed in mice that received OVM and OP, as indicated by reduced colonic pathological scores and pro-inflammatory responses compared with the infected control group. In contrast, OPP consumption resulted in enhanced C. rodentium colonization and disease severity. Notably, reduced microbial diversity indices of the gut microbiota were observed in the OPP-supplemented mice compared with the OVM- and OP-supplemented groups. This study showed the potential of OVM and OP to alleviate the severity of colitis induced by infection while also suggesting the opposite outcome of OPP in mitigating enteric infection.

Asunto(s)

Citrobacter rodentium , Colitis , Infecciones por Enterobacteriaceae , Ratones Endogámicos C57BL , Ovomucina , Animales , Ratones , Femenino , Colitis/inducido químicamente , Colitis/microbiología , Infecciones por Enterobacteriaceae/microbiología , Microbioma Gastrointestinal , Modelos Animales de Enfermedad , Colon/microbiología , Colon/patología , Colon/metabolismo , Hidrolisados de Proteína/farmacología

RESUMEN

κ-Carrageenan is a soluble dietary fiber widely used in meat products. Although its regulatory effect on glycolipid metabolism has been reported, the underlying mechanism remains unclear. The present study established a pork diet model for in vitro digestion to study how κ-carrageenan affected its digestive behavior and lipid bioavailability. The results revealed that κ-carrageenan addition to a pork-based high-fat diet reduced the rate of lipolysis and increased the number and size of lipid droplets in an in vitro digestion condition. However, κ-carrageenan did not inhibit lipolysis when lipids and κ-carrageenan were mixed directly or with the addition of pork protein. Furthermore, the pork protein in the diet significantly enhanced the inhibitory effect of κ-carrageenan on lipolysis with decreased proteolysis and raised hydrophobicity of protein hydrolysate. Our findings suggest that κ-carrageenan can inhibit dietary lipid bioavailability by interacting with pork protein in meat products or meat-based diets during digestion and indicate the positive role of carrageenan in the food industry to alleviate the excessive accumulation of lipids in the body.

Asunto(s)

Disponibilidad Biológica , Carragenina , Dieta Alta en Grasa , Lipólisis , Animales , Porcinos , Lipólisis/efectos de los fármacos , Proteínas de la Carne/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Digestión/efectos de los fármacos , Lípidos/química , Carne de Cerdo/análisis

RESUMEN

Ovarian cancer, a malignant tumor that poses a significant threat to women's health, has seen a rise in incidence, prompting the urgent need for more effective treatment. This study primarily aimed to explore the potential of bovine collagen peptides in inhibiting ovarian cancer. The investigation in this study began with the identification of 268 peptide sequences through LC-MS/MS, followed by a screening process using molecular docking techniques to identify potential peptides capable of binding to EGFR. Subsequently, a series of experiments were performed, demonstrating the inhibitory effects of the peptide GPAGADGDRGEAGPAGPAGPAGPR on the proliferation of ovarian cancer cells. Transcriptomic analysis further revealed that this peptide can regulate cholesterol metabolism in ovarian cancer cells. Finally, a combination of time-resolved fluorescence resonance energy transfer, isothermal titration calorimetry, molecular docking, and molecular dynamics simulations were utilized to validate the ability of this peptide to bind to the epidermal growth factor receptor (EGFR) and impede the binding of epidermal growth factor (EGF) and EGFR.

Asunto(s)

Colágeno , Receptores ErbB , Simulación del Acoplamiento Molecular , Neoplasias Ováricas , Péptidos , Animales , Bovinos , Femenino , Humanos , Secuencia de Aminoácidos , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colágeno/química , Colágeno/farmacología , Receptores ErbB/química , Simulación de Dinámica Molecular , Neoplasias Ováricas/tratamiento farmacológico , Péptidos/química , Péptidos/farmacología , Unión Proteica , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología

RESUMEN

The prevalence of obesity is increasingly widespread, resembling a global epidemic. Lifestyle changes, such as consumption of high-energy-dense diets and physical inactivity, are major contributors to obesity. Common features of this metabolic pathology involve an imbalance in lipid and glucose homeostasis including dyslipidemia, insulin resistance and adipose tissue dysfunction. Moreover, the importance of the gut microbiota in the development and susceptibility to obesity has recently been highlighted. In recent years, new strategies based on the use of functional foods, in particular bioactive peptides, have been proposed to counteract obesity outcomes. In this context, the present study examines the effects of a lupin protein hydrolysate (LPH) on obesity, dyslipidemia and gut dysbiosis in mice fed a high-fat diet (HFD). After 12 weeks of LPH treatment, mice gained less weight and showed decreased adipose dysfunction compared to the HFD-fed group. HFD-induced dyslipidemia (increased triglycerides, cholesterol and LDL concentration) and insulin resistance were both counteracted by LPH consumption. Discriminant analysis differentially distributed LPH-treated mice compared to non-treated mice. HFD reduced gut ecological parameters, promoted the blooming of deleterious taxa and reduced the abundance of commensal members. Some of these changes were corrected in the LPH group. Finally, correlation analysis suggested that changes in this microbial population could be responsible for the improvement in obesity outcomes. In conclusion, this is the first study to show the effect of LPH on improving weight gain, adiposopathy and gut dysbiosis in the context of diet-induced obesity, pointing to the therapeutic potential of bioactive peptides in metabolic diseases.

Asunto(s)

Dieta Alta en Grasa , Disbiosis , Microbioma Gastrointestinal , Resistencia a la Insulina , Lupinus , Obesidad , Hidrolisados de Proteína , Animales , Masculino , Ratones , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Fármacos Antiobesidad/farmacología , Dieta Alta en Grasa/efectos adversos , Dislipidemias/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/tratamiento farmacológico , Hidrolisados de Proteína/farmacología

RESUMEN

Inhibitory activity against angiotensin-converting enzyme (IAACE) by chicken skin collagen hydrolysate (CSCH) and their peptide fractions before and after in-vitro gastrointestinal digestion, were evaluated; as well as their ability to modulate lipid accumulation in 3 T3-L1 adipocytes. Before digestion, peptide fraction <1 kDa (F4) showed the highest IAACE (p < 0.05) followed by CSCH. After these samples were digested, F4 presented an IAACE with IC50 similar to its digest (DF4) (188.84 and 220.03 µg/mL, respectively), which was 2-fold lower (p < 0.05) than IC50 of fraction <1 kDa from post-digested hydrolysate (FDH) (388.57 µg/mL). Nine peptides were identified as the potential ACE inhibitors in F4 and DF4. Addition of DF4 (800 µg/mL) reduced(p < 0.05) lipid accumulation by 83% within preadipocytes. A 45-60% reduction of lipid accumulation within differentiated adipocytes was obtained by adding FDH and DF4 (regardless the concentration). These results, digested CSCH and F4 with IAACE may be considered as potential adjuvants for obesity treatment.

Asunto(s)

Adipocitos , Inhibidores de la Enzima Convertidora de Angiotensina , Pollos , Colágeno , Digestión , Metabolismo de los Lípidos , Péptidos , Hidrolisados de Proteína , Piel , Animales , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Pollos/metabolismo , Ratones , Colágeno/metabolismo , Colágeno/química , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Piel/metabolismo , Piel/química , Péptidos/química , Péptidos/farmacología , Péptidos/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/química , Tracto Gastrointestinal/metabolismo , Células 3T3-L1 , Humanos

RESUMEN

Despite modern advances in food hygiene, food poisoning due to microbial contamination remains a global problem, and poses a great threat to human health. Especially, Listeria monocytogenes and Staphylococcus aureus are gram-positive bacteria found on food-contact surfaces with biofilms. These foodborne pathogens cause a considerable number of food poisoning and infections annually. Ovomucin (OM) is a water-insoluble gel-type glycoprotein in egg whites. Enzymatic hydrolysis can be used to improve the bioactive properties of OM. This study aimed to investigate whether ovomucin hydrolysates (OMHs) produced using five commercial enzymes (Alcalase®, Bromelain, α-Chymotrypsin, Papain, and Pancreatin) can inhibit the biofilm formation of L. monocytogenes ATCC 15313, L. monocytogenes H7962, S. aureus KCCM 11593, and S. aureus 7. Particularly, OMH prepared with papain (OMPP; 500 µg/mL) significantly inhibited biofilm formation in L. monocytogenes ATCC 15313, L. monocytogenes H7962, S. aureus KCCM 11593, and S. aureus 7 by 85.56 %, 80.28 %, 91.70 %, and 79.00 %, respectively. In addition, OMPP reduced the metabolic activity, exopolysaccharide production (EPS), adhesion ability, and gene expression associated with the biofilm formation of these bacterial strains. These results suggest that OMH, especially OMPP, exerts anti-biofilm effects against L. monocytogenes and S. aureus. Therefore, OMPP can be used as a natural anti-biofilm agent to control food poisoning in the food industry.

Asunto(s)

Antibacterianos , Biopelículas , Listeria monocytogenes , Ovomucina , Staphylococcus aureus , Biopelículas/efectos de los fármacos , Listeria monocytogenes/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Ovomucina/farmacología , Ovomucina/metabolismo , Hidrólisis , Adhesión Bacteriana/efectos de los fármacos , Papaína/metabolismo , Pruebas de Sensibilidad Microbiana , Quimotripsina/metabolismo , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/metabolismo

RESUMEN

Baltic herring is the main catch in the Baltic Sea; however, its usage could be improved due to the low processing rate. Previously we have shown that whole Baltic herring hydrolysates (BHH) and herring byproducts hydrolysates (BHBH) by commercial enzymes consisted of bioactive peptides and had moderate bioactivity in in vitro dipeptidyl peptidase (DPP)-4 assay. In this study, we identified the hydrolysate peptides by LC-MS/MS and predicted the potential bioactive DPP-4 inhibitory peptides using in silico tools. Based on abundance, peptide length and stability, 86 peptides from BHBH and 80 peptides from BHH were proposed to be novel DPP-4 inhibitory peptides. BHH was fed to a mice intervention of a high-fat, high-fructose diet to validate the bioactivity. The results of the glucose tolerance and insulin tolerance improved. Plasma DPP-4 activities, C-peptide levels, and HOMA-IR scores significantly decreased, while plasma glucagon-like peptide-1 content increased. In conclusion, BHH is an inexpensive and sustainable source of functional antidiabetic ingredients.

Asunto(s)

Dipeptidil Peptidasa 4 , Inhibidores de la Dipeptidil-Peptidasa IV , Obesidad , Animales , Dipeptidil Peptidasa 4/metabolismo , Ratones , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Obesidad/metabolismo , Masculino , Péptidos , Dieta Alta en Grasa , Peces , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Modelos Animales de Enfermedad , Espectrometría de Masas en Tándem , Hipoglucemiantes/farmacología , Simulación por Computador , Ratones Endogámicos C57BL , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Péptido 1 Similar al Glucagón/metabolismo , Resistencia a la Insulina

RESUMEN

Hypertension is a major controllable risk factor associated with cardiovascular disease (CVD) and overall mortality worldwide. Most people with hypertension must take medications that are effective in blood pressure management but cause many side effects. Thus, it is important to explore safer antihypertensive alternatives to regulate blood pressure. In this study, peanut protein concentrate (PPC) was hydrolyzed with 3-5% Alcalase for 3-10 h. The in vitro angiotensin-converting enzyme (ACE) and renin-inhibitory activities of the resulting peanut protein hydrolysate (PPH) samples and their fractions of different molecular weight ranges were determined as two measures of their antihypertensive potentials. The results show that the crude PPH produced at 4% Alcalase for 6 h of hydrolysis had the highest ACE-inhibitory activity with IC50 being 5.45 mg/mL. The PPH samples produced with 3-5% Alcalase hydrolysis for 6-8 h also displayed substantial renin-inhibitory activities, which is a great advantage over the animal protein-derived bioactive peptides or hydrolysate. Remarkably higher ACE- and renin-inhibitory activities were observed in fractions smaller than 5 kDa with IC50 being 0.85 and 1.78 mg/mL. Hence, the PPH and its small molecular fraction produced under proper Alcalase hydrolysis conditions have great potential to serve as a cost-effective anti-hypertensive ingredient for blood pressure management.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina , Arachis , Peptidil-Dipeptidasa A , Proteínas de Plantas , Hidrolisados de Proteína , Renina , Subtilisinas , Subtilisinas/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Arachis/química , Renina/metabolismo , Renina/antagonistas & inhibidores , Hidrólisis , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacología , Proteínas de Plantas/química , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/química , Antihipertensivos/farmacología , Antihipertensivos/química , Humanos

RESUMEN

This study generated bioactive hydrolysates using the enzyme Alcalase and autolysis from mesopelagic fish, including Maurolicus muelleri and Benthosema glaciale. Generated hydrolysates were investigated for their bioactivities using in vitro bioassays, and bioactive peptides were identified using mass spectrometry in active hydrolysates with cyclooxygenase, dipeptidyl peptidase IV and antioxidant activities. In silico analysis was employed to rank identified peptide sequences in terms of overall bioactivity using programmes including Peptide Ranker, PrepAIP, Umami-MRNN and AntiDMPpred. Seven peptides predicted to have anti-inflammatory, anti-type 2 diabetes or Umami potential using in silico strategies were chemically synthesised, and their anti-inflammatory activities were confirmed using in vitro bioassays with COX-1 and COX-2 enzymes. The peptide QCPLHRPWAL inhibited COX-1 and COX-2 by 82.90% (+/-0.54) and 53.84%, respectively, and had a selectivity index greater than 10. This peptide warrants further research as a novel anti-inflammatory/pain relief peptide. Other peptides with DPP-IV inhibitory and Umami flavours were identified. These offer potential for use as functional foods or topical agents to prevent pain and inflammation.

Asunto(s)

Antiinflamatorios , Proteínas de Peces , Peces , Péptidos , Hidrolisados de Proteína , Animales , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/química , Péptidos/farmacología , Péptidos/química , Péptidos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Proteínas de Peces/farmacología , Proteínas de Peces/química , Antioxidantes/farmacología , Antioxidantes/química , Ciclooxigenasa 2/metabolismo , Simulación por Computador , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/aislamiento & purificación , Ciclooxigenasa 1/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Ciclooxigenasa/química

RESUMEN

The stability of bioactive peptides under various food processing conditions is the basis for their use in industrial manufacturing. This study aimed to identify natural ACE inhibitors with excellent stability and investigate their physicochemical properties and putative molecular mechanisms. Five novel ACE inhibitory peptides (QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ) were isolated and identified using RP-HPLC and Nano LC-MS/MS with foxtail millet protein hydrolysates as the raw material. These peptides are non-toxic and exhibit strong ACE inhibitory activity in vitro (IC50 values between 0.13 mg mL-1 and 0.56 mg mL-1). In addition to QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ have excellent human intestinal absorption. Compared to FPGVSPF and SPAQLLPF, the stable helical structure of LVPYRP and WYWPQ allows them to maintain high stability under conditions that mimic gastrointestinal digestion and various food processing (temperatures, pH, sucrose, NaCl, citric acid, sodium benzoate, Cu2+, Zn2+, K+, Mg2+, Ca2+). The results of molecular docking and molecular dynamics simulation suggest that LVPYRP has greater stability and binding capacity to ACE than WYWPQ. LVPYRP might attach to the active pockets (S1, S2, and S1') of ACE via hydrogen bonds and hydrophobic interactions, then compete with Zn2+ in ACE to demonstrate its ACE inhibitory activity. The binding of LVPYRP to ACE enhances the rearrangement of ACE's active structural domains, with electrostatic and polar solvation energy contributing the most energy to the binding. Our findings suggested that LVPYRP derived from foxtail millet protein hydrolysates has the potential to be incorporated into functional foods to provide antihypertensive benefits.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina , Simulación del Acoplamiento Molecular , Péptidos , Proteínas de Plantas , Hidrolisados de Proteína , Setaria (Planta) , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Setaria (Planta)/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Humanos , Péptidos/química , Péptidos/farmacología , Proteínas de Plantas/química , Proteínas de Plantas/farmacología , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Espectrometría de Masas en Tándem , Simulación por Computador

RESUMEN

Pulses, as an important part of the human diet, can act as a source of high-quality plant proteins. Pulse proteins and their hydrolysates have shown promising results in alleviating metabolic syndrome and modulating the gut microbiome. Their bioactivities have become a focus of research, with many new findings added in recent studies. This paper comprehensively reviews the anti-hypertension, anti-hyperglycemia, anti-dyslipidemia and anti-obesity bioactivities of pulse proteins and their hydrolysates in recent in vitro and in vivo studies, which show great potential for the prevention and treatment of metabolic syndrome. In addition, pulse proteins and their hydrolysates can regulate the gut microbiome, which in turn can have a positive impact on the treatment of metabolic syndrome. Furthermore, the beneficial effects of some pulse proteins and their hydrolysates on metabolic syndrome have been supported by clinical studies. This review might provide a reference for the application of pulse proteins and their hydrolysates in functional foods or nutritional supplements for people with metabolic syndrome.

Asunto(s)

Microbioma Gastrointestinal , Síndrome Metabólico , Hidrolisados de Proteína , Síndrome Metabólico/microbiología , Síndrome Metabólico/dietoterapia , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/administración & dosificación , Animales , Proteínas de Plantas

RESUMEN

Obesity is acknowledged as a significant risk factor for cardiovascular disease, often accompanied by increased inflammation and diabetes. Bioactive peptides derived from marine animal proteins show promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through the AMPK signaling pathway. Therefore, this study aims to investigate the anti-obesity and anti-diabetic effects of bioactive compounds derived from a Meretrix lusoria Protamex enzymatic hydrolysate (MLP) fraction (≤1 kDa) through a 6-week treatment (150 mg/kg or 300 mg/kg, administered once daily) in leptin receptor-deficient db/db mice. The MLP treatment significantly decreased the body weight, serum total cholesterol, triglycerides, and LDL-cholesterol levels while also exhibiting a beneficial effect on hepatic and serum marker parameters in db/db mice. A histological analysis revealed a reduction in hepatic steatosis and epididymal fat following MLP treatment. Furthermore, poor glucose tolerance was improved, and hepatic antioxidant enzyme activities were elevated in MLP-treated mice compared to db/db control mice. Western blot analysis showed an increased expression of the AMPK protein after MLP treatment. In addition, the expression of lipogenic genes decreased in db/db mice. These findings indicate that bioactive peptides, which are known to regulate blood glucose levels, lipid metabolism, and adipogenesis, could be beneficial functional food additives and pharmaceuticals.

Asunto(s)

Fármacos Antiobesidad , Obesidad , Péptidos , Animales , Obesidad/tratamiento farmacológico , Ratones , Masculino , Péptidos/farmacología , Fármacos Antiobesidad/farmacología , Hidrolisados de Proteína/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Hipoglucemiantes/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones Endogámicos C57BL , Receptores de Leptina/metabolismo , Receptores de Leptina/genética , Adipogénesis/efectos de los fármacos , Peso Corporal/efectos de los fármacos

RESUMEN

Bioactive peptides derived from food are promising health-promoting ingredients that can be used in functional foods and nutraceutical formulations. In addition to the potency towards the selected therapeutic target, the bioavailability of bioactive peptides is a major factor regarding clinical efficacy. We have previously shown that a low molecular weight peptide fraction (LMWPF) from poultry by-product hydrolysates possesses angiotensin-1-converting enzyme (ACE-1) and dipeptidyl-peptidase 4 (DPP4) inhibitory activities. The present study aimed to investigate the bioavailability of the bioactive peptides in the LMWPF. Prior to the investigation of bioavailability, a dipeptide YA was identified from this fraction as a dual inhibitor of ACE-1 and DPP4. Gastrointestinal (GI) stability and intestinal absorption of the bioactive peptides (i.e., YA as well as two previously reported bioactive dipeptides (VL and IY)) in the LMWPF were evaluated using the INFOGEST static in vitro digestion model and intestinal Caco-2 cell monolayer, respectively. Analysis of peptides after in vitro digestion confirmed that the dipeptides were resistant to the simulated GI conditions. After 4 hours of incubation, the concentration of the peptide from the apical side of the Caco-2 cell monolayer showed a significant decrease. However, the corresponding absorbed peptides were not detected on the basolateral side, suggesting that the peptides were not transported across the intestinal monolayer but rather taken up or metabolized by the Caco2 cells. Furthermore, when analyzing the gene expression of the Caco-2 cells upon peptide stimulation, a down-regulation of peptide transporters, the transcription factor CDX2, and the tight junction protein-1 (TJP1) was observed, suggesting the specific effects of the peptides on the Caco-2 cells. The study demonstrated that bioactive dipeptides found in the LMWPF were stable through in vitro GI digestion; however, the overall bioavailability may be hindered by inadequate uptake across the intestinal barrier.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina , Dipeptidil Peptidasa 4 , Inhibidores de la Dipeptidil-Peptidasa IV , Absorción Intestinal , Hidrolisados de Proteína , Animales , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Disponibilidad Biológica , Células CACO-2 , Digestión , Dipéptidos/química , Dipéptidos/metabolismo , Dipéptidos/farmacocinética , Dipéptidos/farmacología , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Tracto Gastrointestinal/metabolismo , Absorción Intestinal/efectos de los fármacos , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacocinética , Péptidos/farmacología , Peptidil-Dipeptidasa A/metabolismo , Aves de Corral , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología

RESUMEN

The application of protein hydrolysates (PH) biostimulants is considered a promising approach to promote crop growth and resilience against abiotic stresses. Nevertheless, PHs bioactivity depends on both the raw material used for their preparation and the molecular fraction applied. The present research aimed at investigating the molecular mechanisms triggered by applying a PH and its fractions on plants subjected to nitrogen limitations. To this objective, an integrated transcriptomic-metabolomic approach was used to assess lettuce plants grown under different nitrogen levels and treated with either the commercial PH Vegamin® or its molecular fractions PH1(>10 kDa), PH2 (1-10 kDa) and PH3 (<1 kDa). Regardless of nitrogen provision, biostimulant application enhanced lettuce biomass, likely through a hormone-like activity. This was confirmed by the modulation of genes involved in auxin and cytokinin synthesis, mirrored by an increase in the metabolic levels of these hormones. Consistently, PH and PH3 upregulated genes involved in cell wall growth and plasticity. Furthermore, the accumulation of specific metabolites suggested the activation of a multifaceted antioxidant machinery. Notwithstanding, the modulation of stress-response transcription factors and genes involved in detoxification processes was observed. The coordinated action of these molecular entities might underpin the increased resilience of lettuce plants against nitrogen-limiting conditions. In conclusion, integrating omics techniques allowed the elucidation of mechanistic aspects underlying PH bioactivity in crops. Most importantly, the comparison of PH with its fraction PH3 showed that, except for a few peculiarities, the effects induced were equivalent, suggesting that the highest bioactivity was ascribable to the lightest molecular fraction.

Asunto(s)

Lactuca , Nitrógeno , Hidrolisados de Proteína , Lactuca/metabolismo , Lactuca/genética , Lactuca/efectos de los fármacos , Lactuca/crecimiento & desarrollo , Nitrógeno/metabolismo , Hidrolisados de Proteína/metabolismo , Hidrolisados de Proteína/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Metabolómica , Reguladores del Crecimiento de las Plantas/metabolismo , Transcriptoma/genética , Multiómica