Antihyperglycemic Effects of Salvia polystachya Cav. and Its Terpenoids: alpha-Glucosidase and SGLT1 Inhibitors

The antihyperglycemic activity of ethanolic extract from Salvia polystachya (EESpS) and its products was evaluated using in vivo, ex vivo and in silico assays; additionally, an acute toxicity assay was evaluated. EESpS was classified as a nontoxic class 5 drug. EESpS, ethyl acetate fraction (EtOAcFr), secondary-6-fraction (SeFr6), ursolic acid (UA), and oleanolic acid (OA) reduced the hyperglycemia in DM2 mice. alpha-glucosidase inhibition was evaluated with oral sucrose and starch tolerance tests (OSuTT and OStTT), an intestinal sucrose hydrolysis (ISH) assay and molecular docking studies using acarbose as control. SGLT1 inhibition was evaluated with oral glucose and galactose tolerance tests (OGTT and OGaTT), an intestinal glucose absorption (IGA) assay and molecular docking studies using canagliflozin as the control. During the carbohydrate tolerance tests, all the treatments reduced the postprandial peak, similar to the control drugs. During the ISH, IC50 values of 739.9 and 726.3 mu M for UA and OA, respectively, were calculated. During the IGA, IC50 values of 966.6 and 849.3 for UA, OA respectively, were calculated. Finally, during the molecular docking studies, UA and OA showed increment G values of -6.41 and -5.48 kcal/mol(-1), respectively, on alpha-glucosidase enzymes. During SGLT1, UA and OA showed increment G values of -10.55 and -9.65, respectively.