Inhibition of α-Glucosidase Activity and Islet Amyloid PolyPeptide Fibril Formation by Rubus ulmifolius Fruit Extract: A Potential Therapeutic Approach for Type 2 Diabetes Mellitus

This study examines the antidiabetic potential of Rubus ulmifolius, a shrub traditionally used for medicinal and nutritional purposes. The aim was to assess the fruit extract’s inhibitory effect on α-amylase and α-glucosidase, therapeutic targets in type 2 diabetes (T2D), given their role in carbohydrate digestion. Considering the role of islet amyloid polypeptide (IAPP) aggregation in pancreatic β-cell dysfunction in T2D, the extract’s effect on inhibiting this process was also evaluated. Cytocompatibility and antioxidant effects were tested in Caco-2 cells, while caspase-1 activity was measured to evaluate anti-inflammatory potential. Phytochemical analysis of R. ulmifolius fruits revealed various phenolic compounds, with anthocyanin as the most abundant one. The cyanidin-3-O-glucoside accounted for 86% of all anthocyanins. Among flavonoids, the most represented ones were quercetin-HMGglucoside and a kaempferol derivative, while ellagic acid glucuronide was the predominant ellagitannin. The extract showed significantly higher α-glucosidase inhibition with an IC50 value of 2.8 μg/mL, 32 times more effective than acarbose, and it markedly inhibited IAPP aggregation in a dose-dependent manner. It demonstrated antioxidant activity in cellular and acellular systems, without cytotoxicity. Caspase-1 activity was also reduced in intestinal cells. These findings support R. ulmifolius fruits as a promising functional food for managing T2D and preserving pancreatic function.