Journal Article

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

Cocco, Cristina, Era, Benedetta, Sogos, Valeria, Noli, Barbara, Fais, Antonella, Sanna, Cinzia, Pintus, Francesca, Floris, Sonia, Piras, Franca, De Agostini, Antonio, Di Petrillo, Amalia, Tuberoso, Carlo Ignazio Giovanni, Masala, Valentina

2025

Overview

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-HMG-glucoside 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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Acarbose / Amylin / Anthocyanins / Antidiabetics / Antioxidants / Beta cells / Biocompatibility / Carbohydrates / Caspase-1 / Chronic illnesses / Cytotoxicity / Diabetes / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Ellagic acid / Enzymes / Evaluation / Flavonoids / Fruits / functional food / Functional foods & nutraceuticals / Glucose / Glucosidase / Glucosides / Hyperglycemia / IAPP / Insulin / Kaempferol / Metabolism / Metabolites / Oxidative stress / Phenolic compounds / Phenols / Polypeptides / Prevention / Quercetin / Rubus ulmifolius / Therapeutic targets / type-2 diabetes / wild blackberries / α-Amylase / α-Glucosidase