Antidiabetic effect of Achillea millefollium through multitarget interactions: α-glucosidases inhibition, insulin sensitization and insulin secretagogue activities

Ethnopharmacological importance: Achillea millefolium L. (Asteraceae) is a perennial herb used in Mexican folk medicine for treatment of several pathologies, including inflammatory and spasmodic gastrointestinal disorders, hepatobiliary complaints, overactive cardiovascular, respiratory ailments and diabetes. Aim of the study: To evaluate the potential antidiabetic effect in vivo and to establish the potential mode of action through in vitro approaches of Achillea millefolium. Materials and methods: The antidiabetic effect of hydroalcoholic extract of Achillea millefolium (HAEAm) was evaluated on the oral glucose tolerance tests, in normoglycemic and experimental Type 2 diabetic mice models. In addition, we evaluated the possible mode of action in in vitro assays to determine alpha-glucosidases inhibition, the insulin secretion and calcium mobilization in RINm5F cells and PPAR gamma and GLUT4 expression in 3T3-L1 cells. Results: HAEAm showed significant glucose diminution on oral glucose tolerance test and in acute experimental Type 2 diabetic assay with respect to the control (p < 0.05). In addition, HAEAm promoted the alpha-glucosidases inhibition by 55% at 1 mg/ml respect to control. On the other hand, HAEAm increased the PPAR gamma (five-times) and GLUT4 (two-fold) relative expression than control (p < 0.05). Finally, HAEAm significantly increased the insulin secretion and [Ca2+](i) compared with control. Conclusion: The HAEAm possesses in vivo antidiabetic effect, having such effect through multitarget modes of action that involve antihyperglycemic (alpha-glucosidases inhibition), hypoglycemic (insulin secretion) and potential insulin sensitizer (PPAR gamma/GLUT4 overexpression) actions.