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

Rocio Ortega; Miguel Valdés; Francisco J Alarcón-Aguilar; Ángeles Fortis-Barrera; Elizabeth Barbosa; Claudia Velazquez; Fernando Calzada

doi:10.3390/plants11050575

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

Plants (Basel). 2022 Feb 22;11(5):575. doi: 10.3390/plants11050575.

Authors

Rocio Ortega^{1

2

3}, Miguel Valdés³, Francisco J Alarcón-Aguilar⁴, Ángeles Fortis-Barrera⁴, Elizabeth Barbosa⁵, Claudia Velazquez⁶, Fernando Calzada³

Affiliations

¹ Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, UAM-I, Mexico City CP 09340, Mexico.
² Av. San Rafael Atlixco 186, Leyes de Reforma 1ra Sección, Mexico City CP 09340, Mexico.
³ Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, 2° Piso CORSE Centro Médico Nacional Siglo XXI, IMSS, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, Mexico.
⁴ Laboratorio de Farmacología, Departamento de Ciencias de la Salud, División de CBS, Universidad Autónoma Metropolitana-Iztapalapa, UAM-I, Av. San Rafael Atlixco 186, Leyes de Reforma 1ra Sección, Mexico City CP 09340, Mexico.
⁵ Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón esq. Plan de San Luis S/N, Miguel Hidalgo, Casco de Santo Tomas, Mexico City CP 11340, Mexico.
⁶ Área Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Km 4.5, Carretera Pachuca-Tulancingo, Unidad Universitaria, Pachuca CP 42076, Mexico.

Abstract

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. α-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 µM 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 ∆G values of -6.41 and -5.48 kcal/mol^-1, respectively, on α-glucosidase enzymes. During SGLT1, UA and OA showed ∆G values of -10.55 and -9.65, respectively.

Keywords: SGLT1 inhibitor; Salvia polystachya; acute oral toxicity; antihyperglycemic activity; diabetes mellitus; docking analysis; oleanolic acid; ursolic acid; α-glucosidase inhibitor.