Coconut Milk-Derived Bioactive Peptides as Multifunctional Agents Against Hyperglycemia, Oxidative Stress, and...

Type 2 diabetes mellitus (T2DM) is characterised by chronic hyperglycaemia and accumulation of advanced glycation end products (AGEs), driving interest in food-derived peptides as safer multifunctional modulators. Coconut milk is a promising source, but its anti-hyperglycaemic and anti-glycation potential remains largely unexplored. Here, proteins from coconut cream, skimmed and insoluble fractions of coconut milk were enzymatically hydrolysed, and the resulting peptides were profiled by nano-ESI-Orbitrap-LC-MS/MS. One hundred and fourteen peptides were identified and screened in silico against α-glucosidase, α-amylase, aldose reductase and the receptor for AGEs (RAGE). Two peptides, MQIFVK and ADVFNPR, showed the most favourable docking scores and physicochemical properties. However, ADVFNPR inhibited all 3 diabetic targets & RAGE. Molecular dynamics analysis showed that both peptides bind stably to the diabetic targets. Both peptides were synthesised and evaluated in vitro. ADVFNPR significantly inhibited α-glucosidase, α-amylase and aldose reductase with lower IC₅₀ values and displayed competitive inhibition kinetics. It also scavenged methylglyoxal, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide radicals at low EC₅₀ values, and showed low hemolytic activity in human erythrocytes. These findings indicate that coconut milk contains multifunctional peptides with anti-hyperglycaemic, anti-glycation and antioxidant activities that may be further developed as food-derived adjuncts for managing T2DM and glycation-related complications.