Abstract

Novel dietary strategies are urgently needed to address the limitations of current management and treatment options of Type-2 Diabetes (T2D). Marine algae-derived peptides (MAP) represent a promising avenue, although, their potential remains mostly underexplored. This study employs pharmacoinformatics and in vitro methods to evaluate the antidiabetic properties of MAP and provide new insights their mechanisms to mitigate the prevalence of T2D. Through a systematic search and predictive modeling, peptides were identified and assessed for bioactivity, toxicity, and drug-likeness. Furthermore, molecular docking simulations with protein targets related to T2D identified binding sites that be used to optimize the activity of MAP. The structure-activity relationship profile of MAP reveals 13 candidates with probable activity (Pa) scores >0.4, indicative of insulin promoter. The peptide FDGIP (P13;Phe-Asp-Gly-Ile-Pro) from Caulerpa lentillifera had the best in silico assessment value compared to 50 other peptides and its activity was confirmed by in vitro data (e.g.EC50 60.4 and 57.9 for α-amylase and α-glucosidase inhibitions). Interestingly, in 3T3-L1 cells, P13 exhibited inhibitory activities against transcription factors and hormones (MAPK8-JNK1/PPARGC1A/Ghrelin/GLP-1/CPT-1) that can regulate blood sugar and decrease as anti-diabetes. P13 then appears to be a peptide with antidiabetic action that may be used in the formulation foods to manage T2D.

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