Tofighi Z Moradi-Afrapoli F Ebrahimi SN Goodarzi S Hadjiakhoondi A Neuburger M Hamburger M Abdollahi M Yassa N 2017 Seeds of Securigera securidaca (Fabaceae) are used in Iranian folk medicine as an antidiabetic treatment. In this study, the antihyperglycemic activity of chloroform and methanol fractions (CF and MF) from S. securidaca seed extract was investigated and their bioactive constituents were identified. The antidiabetic effects of fractions were assessed by streptozocin-induced diabetic Naval Medical Research Institute mice. The hypoglycemic activity of MF at 100 mg/kg and CF at 400 mg/kg was comparable with glibenclamide (3 mg/kg). MF at 400 mg/kg and CF at 600 mg/kg showed equal hypoglycemic responses to 12.5 IU/kg insulin (P > 0.05). Three cardiac glycosides were isolated as active constituents responsible for the hypoglycemic activity. Securigenin-3- O -β-glucopyranosyl-(1 → 4)-β-xylopyranoside (1) was a major compound in seeds. Securigenin-3- O -inositol-(1 → 3)-β-glucopyranosyl-(1 → 4)-β-xylopyranoside (2) and securigenin-3- O -α-rhamnopyranosyl-(1 → 4)-α-glucopyranoside (3) were found as new natural products. When 1-3 were tested at 10 mg/kg there was a significant reduction of blood glucose levels in diabetic mice, comparable to that of 3 mg/kg glibenclamide (P > 0.05). The hypoglycemic effect was due to an increase in insulin secretion; the insulin levels in the diabetic mice significantly improved and were comparable with those in healthy animals (P > 0.05). Compounds responsible for the hypoglycemic properties of S. securidaca seeds were identified as cardiac glycosides and were found to act via an increase of insulin levels in a diabetic mouse model. https://sonar.ch/global/documents/159972 eng info:eu-repo/semantics/altIdentifier/doi/10.1007/s11418-016-1060-7 info:eu-repo/semantics/altIdentifier/pmid/27848204 Journal of natural medicines. - 2017 Antidiabetic activity Cardenolides Insulin secretion Securigenin glycosides Securigera securidaca Animals Blood Glucose Diabetes Mellitus, Experimental Fabaceae Hypoglycemic Agents Male Mice Plant Extracts Securidaca Seeds Securigenin glycosides as hypoglycemic principles of Securigera securidaca seeds. http://purl.org/coar/resource_type/c_6501