Protective Effect of Ginseng on Cytokine-Induced Apoptosis in Pancreatic β-Cells

Abstract

The effects of ginseng extracts (GE) and several ginsenosides on cytokine-induced apoptosis were evaluated. In pancreatic beta-cell line MIN6N8 cells, the inhibitory effect of GE was significantly observed at 25-100 microg/mL: an 86-100% decrease of cytoplasmic DNA fragments quantified by an ELISA. The inhibitory effect of red ginseng (RG) extract was greater than that of white ginseng (WG) extract (IC50, 3.633 vs 4.942 microg/mL). Screening of several known ginsenosides, which were present in ginseng extracts at 0.124-1.19% (w/w) by HPLC analysis, revealed that the ginsenosides were responsible for the inhibition of beta-cell apoptosis at 0.1-1.0 microg/mL. The molecular mechanism, by which GE inhibited beta-cell apoptosis, appeared to involve the reduction of nitric oxide (NO) and reactive oxygen species (ROS) production, inhibition on p53/p21 expression, and inhibition on cleavage of caspases and poly(ADP-ribose) polymerase (PARP). This study suggests that ginseng may inhibit cytokine-induced apoptosis in beta-cells and, thus, may contribute via this action to the antidiabetic influence in type 1 diabetes.

Regulation of signaling molecules associated with insulin action, insulin secretion and pancreatic β-cell mass in the hypoglycemic effects of Korean red ginseng in Goto-Kakizaki rats

“…The supplementation also significantly down-regulated the expression of pancreatic UCP2 in GK rats, The present study demonstrated that the supplementation with KRG extract significantly down-regulated the expression of pancreatic Bax in GK rats, suggesting that KRG could increase b-cell mass. Our previous study has shown that KRG extract inhibited the cytokine-mediated activation of PARP in the pancreatic b-cell line MIN6N8 (Kim and Kim, 2007). Consistent with our previous study, the supplementation of KRG extract in this study significantly down-regulated the expression of cleaved PARP from the pancreas in GK rats, suggesting that KRG could increase b-cell mass.…”

“…Protein concentrations were determined using the Bradford protein assay reagent (Quick Start Bradford Dye Reagent) according to the manufacturer's instructions (Bio-Rad Laboratories, Hercules, CA, USA) and 0.1 mg protein was loaded onto a 10% SDS-polyacrylamide gels, separated at 20 mA (100 V), and blotted onto PVDF membranes (Bio-Rad) in Tris borate EDTA buffer. Membranes were incubated for 4 h at room temperature with primary antibodies, and the specific dilutions for each antibody were 1:200 for anti-GLUT4, 1:500 for anti-PTP-1B, 1:200 for anti-insulin, 1:200 for anti-UCP2, 1:1000 for anti-Bax, 1:1000 for anti-cleaved PARP and 1:400 for anti-b-actin (Kim and Kim, 2007). In all cases, the excess of primary antibody was removed by three washes with 50 mM Tris-HCl (pH 7.5, 150 mM NaCl, 0.1% Tween 20); membranes were then incubated with anti-goat or anti-rabbit IgG conjugated with peroxidase (1 mg/ml; Vector Laboratories Inc., Burlingame, CA, USA) for 60 min.…”

“…KRG might mediate its hypoglycemic effect through a variety of mechanisms including actions on the insulin-secreting pancreatic b-cells and the target tissues that take up glucose. In vitro studies have demonstrated that KRG treatment increases insulin secretion from rat islets (Kim and Kim, 2008) and inhibits b-cell apoptosis (Kim and Kim, 2007). It has been reported that KRG administration improved insulin sensitivity in Otsuka Long-Evans Tokushima fatty rats (Lee et al, 2009).…”

Traditional Chinese Medicine in Treatment of Metabolic Syndrome

“…Ginseng was shown to induce expression of anti-apoptotic factor Bcl-2 while suppress expression of pro-apoptotic factor caspase-9 (44). In β-cell line MIN6N8 cells, ginseng extract and ginsenosides were able to inhibit cytokine-induced apoptosis (45). The antioxidant activity of ginsenosides was involved in the anti-apoptosis activity as production of free radicals, such as nitric oxide (NO), and reactive oxygen species (ROS) was reduced by ginsenosides (45).…”

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“…Given its natural product nature, it is possible that the antioxidative properties contribute majorly to the protection of β cells from destruction [39,40] or in some cases, enhancement of pancreatic functions [41], which were shown in other anti-diabetic phytochemical studies. Other studies point to the hypoglycemic or insulinomimetic properties of existing compounds that are naturally derived from plants such as Ficus bengalensis and Lepechinia caulescens [42].…”