In Vitro Alpha-Amylase and Alpha-Glucosidase Inhibitory Activity and In Vivo Antidiabetic Activity of Withania frutescens L. Foliar Extract.

Hamza Mechchate,Dalila Bousta,Abdelhadi Louba,Abdulaziz Alqahtani,Omar M Noman,Imane Es-Safi,Mohammed S Alharbi,Fahd A Nasr,Hicham Bekkari,Ali S Alqahtani,Amina Bari,Muhammad Farooq

doi:10.3390/molecules26020293

Abstract

Withania frutescens L. is a wild perennial woody plant used by the local population for diverse therapeutic purposes. This work aims to study for the first time the potential inhibitory effect of this plant hydroethanolic extract on α-amylase and α-glucosidase activities using in vitro methods and its antidiabetic and antihyperglycemic activities using alloxan-induced diabetic mice as a model for experimental diabetes. Two doses were selected for the in vivo study (200 and 400 mg/kg) and glibenclamide, a well-known antidiabetic drug (positive control) in a subacute study (28 days) where the antihyperglycemic activity was also assessed over a period of 12 h on diabetic mice. The continuous treatment of diabetic mice with the extract of Withania frutescens for 4 weeks succeeded to slowly manage their high fasting blood glucose levels (after two weeks), while the antihyperglycemic test result revealed that the extract of this plant did not control hyperglycemia in the short term. No toxicity signs or death were noted for the groups treated with the plant extract, and it shows a protective effect on the liver and kidney. The in vitro assays demonstrated that the inhibition of alpha-amylase and alpha-glucosidase might be one of the mechanisms of action exhibited by the extract of this plant to control and prevent postprandial hyperglycemia. This work indicates that W. frutescens have an important long term antidiabetic effect that can be well established to treat diabetes.

Highlights

Diabetes mellitus is a chronic condition that affects normal metabolism of carbohydrates, fats, and proteins, triggering numerous changes in the body’s biochemical system that contribute to hyperglycemia, which is the disease’s characteristic [1]
The phytochemical composition and the acute and subacute toxicity of W. frutescens hydroethanolic extract were already being studied in detail in our previous research [12]
Acute oral toxicity of the extract was evaluated in mice according to the Organization of Economic Cooperation and Development (OECD) guidelines 423 [13] with a single oral administration of the extracts at the doses of 400, 1000, and 2000 mg/kg

Summary

Introduction

Diabetes mellitus is a chronic condition that affects normal metabolism of carbohydrates, fats, and proteins, triggering numerous changes in the body’s biochemical system that contribute to hyperglycemia, which is the disease’s characteristic [1]. Multiple synthetic oral hypoglycemic agents are used to overcome elevated blood glucose levels, such as sulfonylureas, biguanides, and inhibitors of alpha-glucosidase. Still, their extended use has revealed more of their several side effects [4] like hypoglycemia, headache, dizziness, nausea, and weight gain [5]. Their extended use has revealed more of their several side effects [4] like hypoglycemia, headache, dizziness, nausea, and weight gain [5] Those side effects made it a priority obligation to find new effective and safer alternatives [6]. In many developed and underdeveloped countries, plants have been used from time immemorial as an alternative form of medication for different physiopathological diseases, including diabetes mellitus [8]

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