{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:39:08Z","timestamp":1791589148575,"version":"4.3.4"},"reference-count":90,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b1-glucosidase, \u03b1-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 &amp; 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 \u03b1-glucosidase, \u03b1-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\u2032-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.<\/jats:p>","DOI":"10.3390\/ijms27010360","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:05:01Z","timestamp":1767193501000},"page":"360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Coconut Milk-Derived Bioactive Peptides as Multifunctional Agents Against Hyperglycemia, Oxidative Stress, and Glycation: An Integrated Experimental and Computational Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Akshaya Simha","family":"Naganarasimha","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7538-311X","authenticated-orcid":false,"given":"Shashank M.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2776-5815","authenticated-orcid":false,"given":"Ramith","family":"Ramu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3399-6129","authenticated-orcid":false,"given":"Maciej","family":"Przyby\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, Pharmacy Faculty, Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, 85096 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7505-6063","authenticated-orcid":false,"given":"Piotr","family":"Be\u0142dowski","sequence":"additional","affiliation":[{"name":"Institute of Computer Science, Kazimierz Wielki University in Bydgoszcz, 85-064 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0812-4396","authenticated-orcid":false,"given":"Olga","family":"Ma\u0142olepsza","sequence":"additional","affiliation":[{"name":"Institute of Computer Science, Kazimierz Wielki University in Bydgoszcz, 85-064 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-5905","authenticated-orcid":false,"given":"S\u0142awomir","family":"Bujanowski","sequence":"additional","affiliation":[{"name":"Faculty of Telecommunications, Computer Science and Electrical Engineering, Bydgoszcz University of Science and Technology, Al. 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