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

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

doi:10.3390/plants11050575

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.

Highlights

Acute oral toxicity assays of the extract from S. polystachya stems were performed according to Guideline 423 of the OECD [37]
Results test (OGTT). (A) OGTT of groups treated with glucose, acarbose, ethanolic extract from Salvia polystachya (EESpS) and EtOAc fraction (EtOAcFr), as we shown as(B)
The present study demonstrates for the first time the isolation of ursolic acid (UA) and oleanolic acid (OA) in S. polystachya

Summary

Introduction

Diabetes mellitus (DM) is a serious chronic disease that occurs when there is no optimal use of insulin in the organism due to a lack of insulin production or because the organism cannot properly use the insulin that is produced due to insulin resistance [1,2]. This alteration in insulin production and utilization is reflected in an increase in the concentration of blood glucose, known as hyperglycemia [3]. Despite the therapeutic effect that is wanted after the administration of the treatments previously described, all of them have side effects such as hypoglycemia, gastrointestinal disorders, diarrhea, nausea, vomiting, abdominal discomfort, flatulence production, and urinary tract infection, among others [11]

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