Pectinase-Processed Ginseng Radix (GINST) Ameliorates Hyperglycemia and Hyperlipidemia in High Fat Diet-Fed ICR Mice

Abstract

To develop a ginseng product possessing an efficacy for diabetes, ginseng radix ethanol extract was treated with pectinase and obtained the GINST. In the present study, we evaluate the beneficial effect of GINST on high fat diet (HFD)-induced hyper-glycemia and hyperlipidemia and action mechanism(s) in ICR mice. The mice were randomly divided into five groups: regular diet group (RD), high fat diet group (HFD), HFD plus GINST at 75 mg/kg (GINST75), 150 mg/kg (GINST150), and 300 mg/kg (GINST300). Oral glucose tolerance test reveals that GINST improves the glucose tolerance after glucose challenge. Fasting plasma glucose and insulin levels were decreased by 4.3% and 4.2% in GINST75, 10.9% and 20.0% in GINST150, and 19.6% and 20.9% in GINST300 compared to those in HFD control group. Insulin resistance indices were also markedly decreased by 8.2% in GINST75, 28.7% in GINST150, and 36.4% in GINST300, compared to the HFD control group. Plasma triglyceride, total cholesterol and non-esterified fatty acid levels in the GINST300 group were decreased by 13.5%, 22.7% and 24.1%, respectively, compared to those in HFD control group. Enlarged adipocytes of HFD control group were markedly decreased in GINST-treated groups, and shrunken islets of HFD control mice were brought back to near normal shape in GINST300 group. Furthermore, GINST enhanced phosphorylation of AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). In summary, GINST prevents HFD-induced hyperglycemia and hyperlipidemia through reducing insulin resistance via activating AMPK-GLUT4 pathways, and could be a potential therapeutic agent for type 2 diabetes.

Keywords: AMP-activated protein kinase; Glucose transporter 4; High fat diet; Insulin resistance; Pectinase-processed ginseng radix.

Fig. 1.. UPLC profiles of ginseng radix (A) and pectinase-processed ginseng radix (GINST) (B). 1: Rg1, 2: Re, 3: Rb1, 4: Rc, 5:Rb2, 6: Rd, 7: IH-901.

Fig. 2.. Plasma glucose responses to an oral glucose challenge (1.5 g/kg) after 12 h food deprivation in ICR mice. Plasma glucose responses to an oral glucose challenge (A) and the area under the curve (AUC) of plasma glucose levels up to 90 min (B). Values are mean ± S.E. (n=5). *p<0.05 compared to HFD control group.

Fig. 3.. Effects of GINST on tissue morphology. Magnification 200x. H&E stainings of epididymal fat pad and pancreas (A). Histomorphometric comparisons of epididymal fat cell size (B) and number of islet cells per section (C). Insulin immunostaining counterstained with hematoxylin (D). **p<0.01 vs. HFO.

Fig. 4.. Effects of GINST on phosphorylated AMPK and GLUT4 protein expression in femoral muscle. **p<0.01 vs. HFO.