α-Glucosidase inhibitory activity and in vitro genotoxic safety of hydrolyzed and non-hydrolyzed fractions from Crocus sativus stamens

The inhibition of intestinal α -glucosidase activity remains an important therapeutic strategy for limiting postprandial hyperglycemia in type 2 diabetes mellitus. In this context, plant-derived inhibitors with safety profiles are receiving increasing attention. Crocus sativus stamens, an underexploited by-product of saffron production, represent a promising source of bioactive compounds. In this study, hydromethanolic and hydroethanolic extracts, along with hydrolyzed and non-hydrolyzed ethyl acetate and aqueous fractions from Crocus sativus stamens, were investigated for their α -glucosidase inhibitory activity in vitro . Antihyperglycemic efficacy was further assessed in vivo using the oral sucrose tolerance test in normal and alloxan-induced diabetic Wistar rats. In addition, the genotoxic safety of fractions was evaluated in rat leukocytes by the alkaline comet assay at concentrations ranging from 25 to 200 µg/mL. Among the tested samples, the hydroethanolic extract and ethyl acetate fractions exhibited pronounced α -glucosidase inhibition, with the hydrolyzed ethyl acetate fraction showing the strongest activity, as reflected by the lowest IC₅₀ value (0.183 ± 0.009 mg/mL) compared to acarbose (IC 50 0.039 ± 0.011 mg/mL). Oral administration of the extracts significantly improved postprandial glycemic responses in both normal and diabetic rats. Genotoxicity assessment revealed no significant DNA damage for most tested fractions at all concentrations, although a slight increase in tail length was observed for the non-hydrolyzed ethyl acetate fraction at 150 µg/mL. Overall, these results demonstrate the potential of Crocus sativus stamens as a promising natural source of α -glucosidase inhibitors with in vitro genotoxic safety profile, supporting their further investigation and valorization as a natural source of natural antidiabetic agents.