Assessing the multitargeted antidiabetic potential of three pomegranate peel-specific metabolites: An in silico and pharmacokinetics study.

Diabetes is a chronic metabolic disorder that occurs due to impaired secretion of insulin, insulin resistance, or both. Recent studies show that the antidiabetic drugs used to control hyperglycemic levels are associated with undesirable adverse effects. Therefore, developing a safe and effective medicine with antidiabetic potential is needed. In this context, in silico studies are considered a rapid, effectual, and cost-effective method in drug discovery procedures. It is evident from the literature that plant-based natural components have shown promising outcomes in drug development to alleviate various diseases and hence have diversified the screening of potential antidiabetic agents. Purposely, in the present study, an in silico approach was performed on three Punica granatum peel metabolites (punicalin, punicalagin, and ellagic acid). All these three compounds were docked against nine protein targets involved in glucose metabolism (GFAT, PTP1β, PPAR-ᵞ, TKIR, RBP4, α-amylase, α-glucosidase, GCK, and AQP-2). These three pomegranate-specific compounds demonstrated significant interactions with GFAT, PTP1β, PPAR-ᵞ, TKIR, RBP4, α-amylase, α-glucosidase, GCK, and AQP-2 protein targets. Specifically, punicalin, punicalagin, and ellagic acid revealed significant binding scores (-9.2, -9.3, -8.1, -9.1, -8.5, -11.3, -9.2, -9.5, -10.1 kcal/mol; -10, -9.9, -8.5, -8.9, -10.4, -9.0, -10.2, -9.4, -9.0 kcal/mol; and -8.1, -8.0, -8.0, -6.8, -8.7, -7.8, -8.3, -8.1, -8.1 kcal/mol, respectively), with nine protein targets mentioned above. Hence, punicalin, punicalagin, and ellagic acid can be promising candidates in drug discovery to manage diabetes. Furthermore, in vivo and clinical trials must be conducted to validate the outcomes of the current study.