Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid

J M Castellano,J Lapetra,J M Santos-Lozano,L Macías,M Rada,A Guinda

doi:10.3989/gya.1237153

Abstract

This work investigates the role of oleanolic acid (OA), isolated from the olive ( Olea europaea L.) leaf, as a radical scavenger and inhibitor of the hydrolyzing enzymes of dietary carbohydrates. New evidence is provided showing that OA may capture 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) and peroxyl radicals, and also exert a strong and non -competitive inhibition of α-glucosidase (IC 50 10.11 ± 0.30 μM). The kinetic and spectrometric analyses performed indicate that OA interacts with this enzyme inside a hydrophobic pocket, through an endothermic and non spontaneous process of a hydrophobic nature. These are two possible mechanisms by which OA may facilitate a better control of post-prandial hyperglycaemia and oxidative stress, so contributing to preserving insulin signalling. Obesity, insulin resistance and Type 2 Diabetes Mellitus are considered the first pandemics of the 21st century. In this sense, OA might be used in future preventive and therapeutic strategies, as an ingredient in new drugs and functional foods.

Highlights

Type 2 Diabetes Mellitus (T2DM), the most common form of the disease affecting near 90% of diabetic people, is recognized as a redox disorder, in which oxidative stress is a primary event underlying insulin resistance, β-cell failure, and longterm diabetes complications (Watson, 2014)
Betulinic acid; hexamethyldisilazane; trimethylchlorosilane; 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS); 2,2-Diphenyl-1-picrylhydrazyl (DPPH); 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH); fluorescein; pancreatic α-amylase; potato starch; 3,5-dinitrosalicylic acid; sodium potassium tartrate; α-glucosidase from Saccharomyces cerevisiae; 4-nitrophenyl-α-D-glucopyranoside (p-NPG); and acarbose were purchased from Sigma-Aldrich (Sigma-Aldrich Quimica, Madrid, Spain)
Eighteen grams and six hundred thirty two milligrams of crystallized oleanolic acid (OA) were obtained from one kilogram of dried olive leaves

Summary

Introduction

Type 2 Diabetes Mellitus (T2DM), the most common form of the disease affecting near 90% of diabetic people, is recognized as a redox disorder, in which oxidative stress is a primary event underlying insulin resistance, β-cell failure, and longterm diabetes complications (Watson, 2014) This prompted investigations on the therapeutic use of antioxidants, none of such studies demon strated clear effects on the metabolic control of diabetic people (Ceriello and Testa, 2009). Salivary and pancreatic α-amylases (EC 3.2.1.1) cleaves the α-(1→4) bonds of starch yielding shorter linear and branched dextrins, which are subsequently hydrolyzed at the non-reducing end into glucose by α-glucosidase (EC 3.2.1.20) in the small-intestinal brush border membrane Synthetic inhibitors, such as acarbose, voglibose or miglitol, are widely used in the clinic. The appearance of adverse effects is frequent, including flatulence, abdominal pain, nausea, vomiting, diarrhea, skin hypersensitivity, an elevation in the hepatic enzymes and even an increased incidence of renal tumors (Fujisawa et al, 2005)

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