Inhibitory effect of aqueous extract from the gall of Rhus chinensis on alpha-glucosidase activity and postprandial blood glucose

Abstract

The present study examined the inhibitory effect of aqueous extract from the gall of Rhus chinensis (AEGRC) on alpha-glucosidase activity, an enzyme responsible for digestion of carbohydrate to monosaccharides in the process of intestinal absorption. AEGRC inhibited Bacillus alpha-glucosidase acitvity with an IC₅₀ of 0.9 μg/ml. Its inhibition on alpha-glucosidase was determined to be noncompetitive and reversible when the enzyme-substrate mixture was simultaneously treated with AEGRC as an inhibitor. In addition, when it was orally administered to rats with sucrose (2 g/kg), AEGRC (250–1000 mg/kg) significantly suppressed the increase of blood glucose levels after sucrose loading in a dose dependent manner. These results suggest that AEGRC might exert anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the postprandial increase of blood glucose.

Introduction

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels. The hyperglycemia is known to be associated with an increased incidence of microvascular complications in patients with type 2 diabetes (Orchard et al., 1997, Corry and Tuck, 2000, Stratton et al., 2000). The recent studies suggested that postprandial hyperglycemia could induce the nonenzymatic glycosylation of various proteins, resulting in the development of chronic complications in diabetes (de Veciana et al., 1995, Lebovitz, 2001). Therefore, control of postprandial plasma glucose levels is critical in the early treatment of diabetes and in reducing chronic vascular complications (Baron, 1998, Lebovitz, 2001). One of the therapeutic approaches for reducing postprandial hyperglycemia is to prevent absorption of carbohydrates after food uptake. Complex polysaccharides must be digested by the enteric digestive enzymes including alpha-glucosidase since only monosaccharides can be absorbed from the intestinal lumen and transported into blood circulation. Therefore, alpha-glucosidase inhibitors such as acarbose, voglibose, and miglitol are widely used either alone, or in combination with insulin secretagogues in patient with type 2 diabetes (Johnston et al., 1998, Saito et al., 1998, Standl et al., 1999). In addition, several alpha-glucosidase inhibitors have been recently developed from the natural sources (Asano et al., 2001, Hiroyuki et al., 2001, Lee and Lee, 2001, Matsui et al., 2001). In the present study, we have examined the inhibitory effect against alpha-glucosidase of aqueous extract of the gall of Rhus chinensis (AEGRC) that have long been used at the Oriental Hospital in Korea for the treatment of patients with so called “So-Gal” symptom, depicting excessive urine excretion and water intake. We found that AEGRC, known as “Obaeja” in Korea, suppressed significantly alpha-glucosidase activity. Furthermore, we carried out in vitro experiments including kinetics of enzyme inhibition as well as in vivo monitoring for blood glucose level after sucrose loading in order to elucidate mode of inhibitory action and postprandial anti-hyperglycemic effect of AEGRC.