Modulation of Glycemic Control by Vaccinium myrtillus Leaf Extract: Impact of Inulin Co-Administration

<i>Vaccinium myrtillus</i> L. (bilberry) leaves have traditionally been used to manage hyperglycaemia in folk medicine. The combination of plant polyphenols with dietary fibres such as inulin may offer enhanced metabolic benefits; however, their combined effects remain insufficiently characterized. This study aimed to evaluate the antihyperglycaemic effects of bilberry leaf extract (VME) and its inulin-enriched formulation (VMEI), and to investigate their potential as functional food components for managing type 2 diabetes. VME and VMEI were assessed using in vitro enzyme inhibition and an in vivo <i>Caenorhabditis elegans</i> model to evaluate toxicity. High-performance liquid chromatography (HPLC) was used to profile major compounds. A three-month dietary intervention was conducted in mice fed a high-fat, high-sucrose (HFHS) diet to examine the glucose-lowering effects of the extracts. HPLC analysis identified chlorogenic acid as the major constituent, followed by quercetin derivatives. VMEI exhibited stronger α-glucosidase inhibition than VME, indicating synergistic activity. Rutin and hyperoside showed the highest inhibitory activity against α-amylase and α-glucosidase, respectively. In <i>C. elegans</i>, VME displayed moderate toxicity at higher doses, and both extracts reduced locomotion. In the mouse model, both VME and VMEI significantly reduced blood glucose levels in HFHS-fed mice, with effects comparable to healthy control. VMEI showed more pronounced improvements, still not statistically significant. Overall, the combination of bilberry leaf polyphenols with inulin demonstrated enhanced in vitro enzyme inhibition, while in vivo findings indicate potential antihyperglycaemic effects that warrant further investigation. These results support the continued exploration of VMEI as a functional food candidate for metabolic health management.