Hypoglycemic and Hypolipidemic Potentials of Ananas comosus (Linn.) Merr. Fruit Peel: An In Silico Modelling and In Vivo Analysis

Introduction: Diabetes mellitus (DM) is a non-communicable, complex disorder that affects all groups of people, whether young, old, short, tall, black, white, male, or female, and it is still without a cure. Medicinal plants, functional foods, and their waste products are known veritable sources of antidiabetic drugs. This study investigated the blood glucose-lowering (hypoglycemic) and lipid-lowering (hypolipidemic) effects of Ananas comosus aqueous-ethanol fruit peel extract (ACAPE) using in-silico and in vivo methodologies. Methods: The in-silico (site-specific and blind) molecular docking assessed the interaction of ACAPE bioactive compounds with diabetic-related protein targets, specifically human α-amylase and aldose reductase, using PyRx, AutoDock Vina, and Biovia Discovery Studio. Animals were made diabetic using 60 mg/kg body weight streptozotocin (STZ) and later treated for 28 days, sacrificed, and blood collected for biochemical parameter evaluation using standard procedures and kits: glucose and protein concentrations; lipid profile levels; and hepatic antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT) and he-patic function (alanine (ALT) and aspartate (AST) transaminases) activities. Results: The results indicated that ACAPE had abundant polyphenolics. Treatment of dia-betic animals with ACAPE restored the dysfunction in glucose and lipid concentrations and significantly (p<0.05) increased the hepatic function and antioxidant enzyme activities in diabetic animals. 2-Chloro-4-(4-methoxyphenyl)-6-(4-nitrophenyl) pyrimidine (-10.5 kcal/mol) and α-muurolene (-8.9 kcal/mol) showed overall good binding energy and affinity against aldose reductase and α-amylase in silico. Discussion: This study highlights the antidiabetic potential of Ananas comosus peel extract, which significantly improved blood glucose, lipid profile, liver enzymes, and antioxidant activities in diabetic rats. The in-silico results also showed strong interactions between key phytochemicals and diabetic-related enzymes, supporting the observed biological effects. However, this study is limited by the absence of mechanistic studies such as gene/protein expression, a lack of histopathological evaluation, dose optimization, and a lack of clinical human studies to confirm these findings. Conclusion: It can be concluded from the findings of this study that ACAPE is rich in phy-tochemical constituents, especially polyphenolics, that can be explored for the treatment of diabetes and its related complications.