Beneficial Effects of Small Molecule Oligopeptides Isolated from Panax ginseng Meyer on Pancreatic Beta-Cell Dysfunction and Death in Diabetic Rats

Abstract

To determine whether treatment with ginseng oligopeptides (GOPs) could modulate hyperglycemia related to type 2 diabetes mellitus (T2DM) in rats induced by high-fat diet and low doses of alloxan, type 2 diabetes was induced in male Sprague-Dawley (SD) rats by injecting them once with 105 mg/kg alloxan and feeding them high-carbohydrate/high-fat diet with or without GOP administration (0.125, 0.5, and 2.0 g/kg Body Weight) for 7, 24, and 52 weeks. Oral glucose test tolerance (OGTT), plasma glucose, serum insulin, level of antioxidant, and beta cell function were measured. Morphological observation and immunohistochemistry study of insulin of islets was performed by light microscopy. The insulin level and the expression of NF-κB and Bcl-2 family in pancreatic islets were also detected by Western blot analysis. In addition, survival time and survival rate were observed. After the treatment, the abnormal OGTT were partially reversed by GOPs treatment in diabetic rats. The efficacy of GOPs was manifested in the amelioration of pancreatic damage, as determined by microscopy analysis. Moreover, GOPs treatment increased the normal insulin content and decreased the expression of the NF-κB-signaling pathway. Compared with those in the control model, the survival time and rate were significantly longer. It is suggested that GOPs exhibit auxiliary therapeutic potential for diabetes.

Keywords: Panax ginseng oligopeptide; alloxan; high-carbohydrate/high-fat; pancreatic beta-cell failure; type 2 diabetes mellitus.

Figure 1

Schematic representation of the experimental procedures. The present study was performed in Sprague–Dawley rats made diabetic with low dose alloxan and a high-carbohydrate/high-fat diet. GOPs: Panax ginseng oligopeptide; OGTT: oral glucose tolerance test. NC, normal control group; MC, model control group; GOPs-L, low dose of GOPs-treated group; GOPs-M, medium dose of GOPs-treated group; GOPs-H, high dose of GOPs-treated group.

Figure 2

Effects of Panax ginseng oligopeptide (GOPs) on survival time in rats. 15 rats/group were used in each group (log-rank test, χ² = 12.706, p = 0.013). NC, normal control group; MC, model control group; GOPs-L, low dose of GOPs-treated group; GOPs-M, medium dose of GOPs-treated group; GOPs-H, high dose of GOPs-treated group.

Figure 3

Effect of GOPs on OGTT in normal and diabetic rats. 8 rats/group (at week 7) and 6 rats/group (at week 52) were used in each group. The data were analyzed for significance of differences by one-way analysis of variance test. ^a p < 0.05 versus NC rats, ^b p < 0.05 versus MC rats. FBG, fasting blood-glucose; GOPs, Panax ginseng oligopeptides; OGTT, oral glucose tolerance test; OGTT-AUC, OGTT-area under curve. NC, normal control group; MC, model control group; GOPs-L, low dose of GOPs-treated group; GOPs-M, medium dose of GOPs-treated group; GOPs-H, high dose of GOPs-treated group.

Figure 4

Effect of Panax ginseng oligopeptide (GOPs) on NF-κB, Bax, Bcl-2 and cleaved Caspase-3 activation in the pancreas of normal and diabetic rats at week 7. 8 rats/group were used in each group. beta-actin protein levels were used as a control. The ratios were calculated as means ± SEM of three determinations from three individual rats in each group. ^a p < 0.05 versus NC rats, ^b p < 0.05 versus MC rats. NC, normal control group; MC, model control group; GOPs-L, low dose of GOPs-treated group; GOPs-M, medium dose of GOPs-treated group; GOPs-H, high dose of GOPs-treated group.

Figure 5

Effect of GOPs on pancreatic histopathology (A) and immunohistochemistry study (B) on insulin of islets in normal and diabetic rats. 6 rats/group were used in each group. NC, normal control group; MC, model control group; GOPs-L, low dose of GOPs-treated group; Scale bar = 50 μm.

Figure 6

Effect of GOPs on liver and kidney profiles in normal and diabetic rats. 8 rats/group (at week 7) and 6 rats/group (at week 52) were used in each group. The data were analyzed for significance of differences by one-way analysis of variance test. ^a p < 0.05 versus NC rats, ^b p < 0.05 versus MC rats. ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; GOPs, Panax ginseng oligopeptides; Scr, serum creatinine; TC, total cholesterol; TG, triglyceride. NC, normal control group; MC, model control group; GOPs-L, low dose of GOPs-treated group; GOPs-M, medium dose of GOPs-treated group; GOPs-H, high dose of GOPs-treated group.