Integrated Computational and Experimental Assessment of Food Derived Bioactive Peptides as Potential Therapeutics for Diabetes Induced Platelet Hyperaggregation

Abstract

Background: Diabetes mellitus induces a state of "sticky" blood, where chronic hyperglycemia triggers oxidative stress and receptor dysregulation, leading to platelet hyperaggregation. This pro-thrombotic environment is a primary driver of myocardial infarction (MI). While synthetic antiplatelet agents are standard, their use is often limited by bleeding risks and gastrointestinal toxicity. Food-derived bioactive peptides (BAPs) and phytochemicals from medicinal plants like Terminalia arjuna offer a multi-target, lower-toxicity alternative. Objective: This review aims to integrate modern computational peptidomics with classical experimental pharmacology to evaluate the therapeutic potential of BAPs in mitigating diabetes-induced platelet dysfunction. Methods: We synthesize recent findings (2021–2026) focusing on in silico database mining (e.g., BIOPEP-UWM) and molecular docking against key thrombotic targets such as P2Y12, COX-1, and GP IIb/IIIa. The review further assesses experimental validation using the Isoproterenol (ISO)-induced MI model to demonstrate the cardioprotective and anti-aggregatory efficacy of these compounds in vivo. Results: Integrated assessments reveal that BAPs from dairy, marine, and specifically Terminalia arjuna sources inhibit the polyol pathway and NADPH oxidase activity, thereby reducing ROS-mediated platelet activation. Furthermore, nano-delivery systems—including liposomes and chitosan nanoparticles—have shown significant success in overcoming the inherent bioavailability barriers and proteolytic degradation of these peptides. Conclusion: The synergy between computational screening and the ISO-induced MI model provides a robust pipeline for the discovery of novel peptide therapeutics. Terminalia arjuna emerges as a dual-action candidate, providing both metabolic regulation and direct antiplatelet effects, potentially bridging the gap between nutraceuticals and pharmaceutical-grade anticoagulants.