Hypoglycemic Efficacy of Docking Selected Natural Compounds against α-Glucosidase and α-Amylase

Abstract

The inhibition of α-glucosidase and α-amylase is a clinical strategy for the treatment of type II diabetes, and herbal medicines have been reported to credibly alleviate hyperglycemia. Our previous study has reported some constituents from plant or herbal sources targeted to α-glucosidase and α-amylase via molecular docking and enzymatic measurement, but the hypoglycemic potencies in cell system and mice have not been validated yet. This study was aimed to elucidate the hypoglycemic efficacy of docking selected compounds in cell assay and oral glucose and starch tolerance tests of mice. All test compounds showed the inhibition of α-glucosidase activity in Caco-2 cells. The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice after OGTT and OSTT, respectively and the decreased glucose levels of test compounds were significantly varied in acarbose. Taken altogether, in vitro and in vivo experiments suggest that selected natural compounds (curcumin, antroquinonol, HCD, docosanol, tetracosanol, rutin, and actinodaphnine) via molecular docking were confirmed as potential candidates of α-glucosidase and α-amylase inhibitors for treating diabetes.

Keywords: natural compound; α-amylase; α-glucosidase.

Figure 1

Cytotoxicity of selected compounds on Caco-2 cells. The cell viabilities were treated with various concentration of (A) acarbose, catechin, quercetin, rutin, (B) curcumin, 16-hydroxycleroda-3,13-dien-16,15-olide (HCD), (C) docosanol, tetracosanol, and (D) antroquinonol, berberine, and (E) actinodaphnine in Caco-2 cells measured via MTT assay and shown as the mean ± SD. * p < 0.05 when compared with the untreated control group (0 µM); NS, not significant.

Figure 1

Cytotoxicity of selected compounds on Caco-2 cells. The cell viabilities were treated with various concentration of (A) acarbose, catechin, quercetin, rutin, (B) curcumin, 16-hydroxycleroda-3,13-dien-16,15-olide (HCD), (C) docosanol, tetracosanol, and (D) antroquinonol, berberine, and (E) actinodaphnine in Caco-2 cells measured via MTT assay and shown as the mean ± SD. * p < 0.05 when compared with the untreated control group (0 µM); NS, not significant.

Figure 2

Inhibitory effect of test compounds on the in vitro maltose digestion. Caco-2 cells were treated with test compounds (acarbose (Aca) 40 or 80 μM; antroquinonol (Ant) 5 or 10 μM; catechin (Cat) 40 or 80 μM; quercetin (Que) 40 or 80 μM; actinodaphnine (Act) 40 or 80 μM; curcumin (Cur) 10 or 40 μM; docosanol (Doc) 40 or 80 μM; tetracosanol (Tet) 40 or 80 μM; rutin (Rut) 40 or 80 μM; berberine (Ber)10 or 40 μM; 16-hydroxycleroda-3,13-dien-16,15-olide (HCD) 5 or 10 μM) and maltose for (A) 6 h, (B) 12 h, and (C) 24 h prior to analyze glucose concentration in culture medium. The data are presented as mean ± SD. * p < 0.05 as compared with maltose alone.

Figure 3

Hypoglycemic effects on oral administration of glucose or starch with acarbose or natural compounds in mice. 4.0 g/(kg·B.wt.) of glucose (OGTT) or 2.5 g/(kg·B.wt) of starch (OSTT) mixed with single dose of natural compounds (acarbose (Aca) 17 mg/kg, curcumin (Cur) 0.3 mg/kg, 16-hydroxycleroda-3,13-dien-16,15-olide (HCD) 3 mg/kg, docosanol (Doc) 4 mg/kg, tetracosanol (Tet) 4 mg/kg, antroquinonol (Ant) 1 mg/kg, berberine (Ber) 100 mg/kg, catechin (Cat) 6 mg/kg, quercetin (Que) 60 mg/kg, actinodaphnine (Act) 5 mg/kg, and rutin (Rut) 4 mg/kg) were oral gavaging followed by blood sampling every 30-min interval until 120 min, respectively. (A) Increasing blood sugar as compared with initial; (B) The ratio to starch; and (C) The ratio to glucose was calculated and compared. * p < 0.05 when compared with acarbose during glucose or starch given.