La creciente demanda de alimentos de alto valor nutricional ha inclinado el consumo de lácteos de leche bovina por leche proveniente de otras especies de rumiantes; no obstante, la fracción proteica de la leche es relativamente constante y se compone de caseínas: S1-caseína, -caseína, 𝜅-caseína, y seroproteínas; -lactoalbúmina y -lactoglobulina. En la actualidad, los estudios de péptidos bioactivos derivados de la leche se centran en proteínas obtenidas de una única especie y se efectúan empleando enzimas ajenas al sistema digestivo humano. La presente investigación realizó una comparación cuantitativa de los péptidos bioactivos obtenidos de las caseínas y seroproteínas presentes en la leche de bovino (Bos taurus), oveja (Ovis aries), cabra (Capra hircus) y búfalo (Bubalus bubalis) a partir de procesos de digestión in silico catalizados por proteasas presentes en el sistema digestivo humano: pepsina (EC 3.4.23.1), tripsina (EC 3.4.21.4) y quimotripsina (EC 3.4.21.1). La caracterización de péptidos bioactivos y la digestión in silico fue realizada mediante BIOPEP-UMW. La evaluación cuantitativa se efectuó a partir del cálculo de frecuencias de liberación. Los resultados mostraron once clases de péptidos con acción biológica: estimulantes, inhibidores de Renina, inhibidores de DPP4, antioxidantes, inhibidores de ACE, inhibidores de DPP3, hipocolesterolémicos, inhibidores de CaMPDE, reguladores, anticancerígenos e inmunomoduladores. Los péptidos inhibidores de DPP4 presentaron la mayor frecuencia de liberación, lo que sitúa a la leche como una potencial fuente de metabolitos supresores de la acción proteolítica de DPP4 en la degradación de incretinas. Pese a los distintos valores de frecuencias de liberación, los cuatro perfiles totales de péptidos bioactivos correspondientes a la leche de cada especie no mostraron una diferencia estadísticamente significativa (p>0.05).
Background: Milk-derived biopeptides have reported in vitro dipeptidyl-peptidase IV (DPP-IV) inhibition, suggesting a glycemic-regulatory effect in Type 2 Diabetes Mellitus (T2DM). Nonetheless, the therapeutic application of these nutraceuticals is limited by the scarcity of knowledge regarding their pharmacokinetic profile. Objective: This study aimed to characterize and assess the pharmacokinetics of milk-derived biopeptides. Through an in silico comparative analysis with gliptins, we expected to identify enhanced properties in food-hydrolysates and suitable DPP-IV inhibiting peptides as candidates for T2DM therapy. Methods: A comparison between gliptins and biopeptides was conducted based on in silico evaluation of drug-likeness, physicochemical properties, pharmacokinetics, and synthetic accessibility. Suitable target proteins for gastrointestinal-absorbable biopeptides were determined as well. Data collection was performed on SwissADME, ADMETlab, DrugBank, SwissTargetPrediction, ChemDes, and BIOPEP-UWM platforms. Statistical analysis was carried out using a one-way ANOVA test. Results: Drug-likeness compliance showed no significant difference between gliptins and biopeptides (p>0.05) in three out of nine assessed rules, though gastrointestinal-absorbable biopeptides exhibited no significant difference with gliptins in five drug-likeness guidelines. The physicochemical evaluation revealed a significant difference (p<0.05) between both groups, with peptides exhibiting enhanced solubility, flexibility, and polarity. Nine out of thirty-six assessed biopeptides reported being likely gastrointestinal-absorbable molecules, from which six displayed ≥30% predicted bioavailability, two reported CYP450 interactions, and all were determined to be blood confined. Biopeptides showed a slightly lower clearance than gliptins yet counteracted by a significantly lower half-life. Moreover, synthetic accessibility scores indicated higher synthetic ease for biopeptides. In addition, absorbable bioactive peptides reported a considerable binding affinity to DPP-IV and Calpain-I. Conclusions: Compared to gliptins, gastrointestinal-absorbable biopeptides exhibit superior physicochemical properties (higher solubility, flexibility, and polarity), lesser CYP450 interactions, higher synthetic ease, and some reported an important affinity for DPP-IV and Calpain-I. Only a small fraction of milk-derived biopeptides are suitable drug-like compounds and feasible candidates for T2DM therapy; yet, testing their therapeutic potency remains subject to further studies.
Background : The nutraceutical properties of food hydrolysates rely on multiple biochemical interactions involving the modulation of enzymes and cellular receptors. Numerous bioactive peptides released from troponin and tropomyosin digestion have been identified. Their characterization has mostly been performed by hydrolysis catalyzed by proteases unrelated to the human digestive system. Objective: This study aimed to determine the bioactive profile of beef, pork, and chicken meat by analyzing the frequency and pharmacokinetics of biopeptides released from troponin and tropomyosin. Methods: In silico digestion and biopeptide release frequency were studied by three parameters; bioactive fragments release frequency (AE), frequency percentage (W), and mean occurrence (AS), all stated on the BIOPEP-UWM platform. Further on, hydrolysis end-products were screened based on gastrointestinal-absorption probability and pharmacokinetic profiling performed on SwissADME, SwissTargetPrediction, and ADME/Tlab bioinformatics web tools. Statistical analyses were performed using a one-way ANOVA test. Results: Dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibiting biopeptides exhibited the highest release frequency. Moreover, W and AS parameters showed no significant difference (p>0.05) between the myofibrillar isoforms assessed. Seven biopeptides were classified as highly absorbable and reported optimal drug-likeness compliance. Although biopeptides hold good pharmacokinetic properties, the therapeutic potency of biopeptides showed to be lower than those of DPP-IV and ACE-inhibiting drugs. Conclusions: Troponin and tropomyosin are rich dietary sources of bioactive peptides, mainly DPP-IV and ACE inhibitors. Digestion end-products are mainly dipeptides with optimal pharmacokinetic and drug-like properties, suggesting a potential therapeutic application in hypertensive and hyperglycemic disorders.
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