To evaluate the dichloromethane extract of Ficus carica leaves (FCL) had a hypoglycemic impact in diabetic mice, as well as to identify the bioactive components in the extract and analyze their anti-hyperglycemia potential in HepG2 cells. The antidiabetic activity of dichloromethane extract of Ficus carica leaves was evaluated in diabetic mice induced by streptozotocin (STZ,100 mg/kg) combined with high-fat diet. The fasting blood glucose (FBG), blood lipids, oral glucose tolerance, glycated hemoglobin (HbA1c), and pathological change effects of the extract were measured after administering two doses of the extract (500 and 1000 mg/kg). On the other hand, we used column chromatography to isolate the dichloromethane extract, and we structurally identified the compounds based on 1H NMR and 3C NMR spectra. The hypoglycemic activity of isolated compounds was investigated in palmitic acid (PA)-induced HepG2 cells. FCL extract lowers blood glucose and improves blood lipids and the pancreatic β-cell also tend to recover whether the psoralen is removed or not. Meanwhile, three coumarins except psoralen were isolated from dichloromethane extract: 3,4-dihydropsoralen, umbelliferone and 7-hydroxyl-6-methylcoumarin. Psoralen and umbelliferone promoted glucose uptake in HepG2 cells. In vivo experiments, dichloromethane extract of FCL has potential antidiabetic activity, mainly by lowering blood glucose, improving blood lipids, glucose tolerance and repairing pancreatic islet damage, which justifies its use in the treatment of diabetes in Spanish folklore. Additionally, in vitro experiments, psoralen and umbelliferone demonstrated substantial glucose-lowering activity.
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