Anti-hyperglycemic effect of two terpenoids isolated from Coula edulis on normoglycemic rats and in silico study of their potential inhibitors on α-amylase and dipeptidylpeptidase 4

Abstract

Diabetes causes many deaths around the world, making the search for treatments a real challenge. Plant secondary metabolites are promising candidates because they act as scaffolds in biological processes. This study investigates anti-hyperglycaemic effect of two terpenoids isolated from Coula edulis and in silico study of their potential inhibitors on α-amylase and dipeptidypeptidase 4. After extraction and isolation of the two terpenoids, their structures were characterized using 1D and 2D NMR spectroscopic techniques. Subsequently the anti-hyperglycemic effect was achieved following an overload of starch on the one hand and glucose on the other hand in normoglycemic rats. Each isolated terpenoids was tested at a dose of 3 mg/kg.bw, the same for the reference compounds (Acarbose and glibenclamide). Conformational site analysis and docking parameters such as binding energy, inhibition constant, interaction profiles with diabetes target residues (α-amylase and dipeptidypeptidase 4) were determined using AutoDock 4.2 and Discovery Studio visualizer. The results showed that the terpenoids isolated from coula edulis were Taraxerol and 3β-(Z)-coumaroyltaraxerol, each of its two terpenoids considerably decreased the blood sugar levels in rats after overloading of starch and glucose solutions respectively. Their effects were similar to the reference drugs. Furthermore, the in-silico approach showed that these compounds have good docking scores with α-amylase and with DPP4. Taraxerol exhibited a docking score more than three times than the acarbose docking score. Only 3β-(Z)-coumaroyltaraxerol reacts with at least one amino acid of the α-amylase catalytic triad (Asp 300). Both interact with histidine (His 740) of the DPP4 catalytic triad. In view of this results, taraxerol and 3β-(Z)-coumaroyltaraxerol have anti-hyperglycemic effects and are good candidates for the development of new multitarget antidiabetics.
 Keywords: Coula edulis, RMN 1D and 2D, tarxerol, 3β-(Z)-coumaroyltaraxerol and Anti-hyperglycemia