Characterizing the Antihyperglycemic Activity and Underlying Mechanisms of the Aqueous Extract of the Leaves from Ficus carica L.

Ficus carica L. is traditionally used for diabetes management. This study evaluated the antihyperglycemic activity, safety, possible mechanisms, and phytochemical composition of its aqueous leaf extract (EAcFc). EAcFC activity was evaluated in streptozotocin–nicotinamide-induced type 2 diabetic (ST2D) mice under acute and subchronic conditions. EAcFc showed low acute toxicity (LD50 > 3000 mg/kg). Acute and subchronic oral administration of EAcFc (300 mg/kg) significantly reduced blood glucose levels in ST2D mice. Although sustained HbA1c reduction was not observed, EAcFc improved lipid profiles, notably reducing triglyceride concentrations in ST2D males (from 156 ± 19.4 to 89.7 ± 3.3 mg/dL at week 4) and females (from 138 ± 2.0 to 77 ± 16.0 mg/dL at week 4). In oral sucrose and lactose tolerance tests (3 g/kg load), EAcFc (300 mg/kg) significantly attenuated postprandial hyperglycemia at 30, 60, and 120 min, an effect comparable to acarbose (50 mg/kg). No significant activity was observed during the oral glucose tolerance test (1.5 mg/kg load), suggesting the effect is not mediated by SGLT-1 inhibition. Preparative TLC and NMR analysis identified narcissin, nicotiflorin, and β-sitosterol. Thus, EAcFc possesses antihyperglycemic and lipid-modulating properties partially associated with α-glucosidase inhibition and bioactive flavonoids and phytosterol.