In Vivo and In Silico Analysis of Quercetin’s Effects on Glycemic Regulation

Abstract

Background & Objective Diabetes mellitus is a global health issue caused by chronic hyperglycemia. Although various therapeutic options are available, each carries potential side effects, prompting growing interest in exploring natural compounds as alternative treatments. Quercetin, a flavonoid known for its antioxidant and anti‐inflammatory properties, is suspected to play a role in glucose regulation, although its molecular mechanisms remain incompletely understood. This study aimed to analyze the in vivo effects of quercetin on the phenotype of Drosophila melanogaster and to validate its potential mechanism through an in silico molecular docking approach, focusing on its interaction with diabetes‐related enzyme targets. Methods Phenotypic evaluation included measurements of body morphology, locomotor activity, survival rate, and hemolymph glucose levels. Molecular analyses were conducted using reverse transcription quantitative PCR (RT‐qPCR), while molecular docking studies were performed to assess quercetin’s interaction with the enzyme dipeptidyl peptidase‐4 (DPP4). Results Quercetin significantly reduced hemolymph glucose levels in both larvae ( p < 0.0001) and adult flies ( p < 0.001) within the concentration range of 1–10 μm without affecting adult flies’ locomotor activity or survival. Additionally, quercetin enhanced the expression of genes involved in metabolic and stress response and improved growth parameters and motor activity in larvae subjected to a high‐sugar diet. Molecular docking studies revealed that quercetin has a high affinity for DPP4, supporting its proposed hypoglycemic mechanism. Conclusion This study provides both phenotypic and molecular evidence that quercetin exerts hypoglycemic effects in D. melanogaster , potentially mediated through DPP4 inhibition and modulation of metabolic and stress‐response pathways. These findings offer new insight into the mechanisms of quercetin in glucose regulation.

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