Postprandial glycemic effects, acute oral tolerability, and exploratory DNA-damage assessment of an aqueous Anethum graveolens L. seed extract

Anethum graveolens L. (dill) has a long history of medicinal use and has been investigated for potential glucosemodulating properties; however, evidence regarding its acute effects on postprandial glycemia and its toxicological profile remains limited.This study evaluated the acute oral tolerability, DNA-damaging potential, and postprandial glycemia-modulating effects of an aqueous seed extract of A. graveolens (AGAE).The extract was prepared by decoction from seeds purchased in the Béni Mellal-Khénifra region of Morocco.Acute oral toxicity was assessed in Swiss albino mice after single oral doses of 0.5, 1, and 2 g/kg followed by a 14-day observation period.DNA-damage responses were explored ex vivo in leukocytes obtained from a single male Wistar rat using the alkaline comet assay after exposure to AGAE concentrations ranging from 1 to 100 µg/mL.The effects of AGAE (400 mg/kg, p.o.) on postprandial glycemia were investigated in normoglycemic mice using oral glucose, sucrose, and starch tolerance tests, with glibenclamide and acarbose as reference drugs.In the glucose tolerance test, AGAE significantly reduced blood glucose at 60 min (p < 0.001), although the overall area under the curve (AUC) was not significantly affected.Following sucrose loading, AGAE did not significantly alter blood glucose concentrations or the AUC.In contrast, after starch loading, AGAE significantly reduced blood glucose at 60, 90, and 150 min (p < 0.001) and significantly decreased the AUC (p < 0.001).No mortality or overt clinical or behavioral signs of acute toxicity were observed at doses up to 2 g/kg.In the comet assay, no clear concentration-dependent pattern was observed across the evaluated DNA-damage descriptors, although higher tail-length and % tail-DNA values were observed at 100 µg/mL.Overall, AGAE exhibited acute glycemia-modulating activity in normoglycemic mice, with the most pronounced effect observed following starch loading, while showing no overt acute oral toxicity at the tested doses.Further studies are required to clarify the mechanisms underlying its effects on starch-derived glycemia and to characterize its genotoxic and repeated-dose safety profiles.