Abstract
We investigated anti-hyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On Day 5, 150 mg/kg extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice $(156{\pm}9.0\;mg/dl\;vs.\;243{\pm}15.8mg/dl,$ P<0.01). On Day 12, the extract-treated ob/ob mice became normoglycemic $(137{\pm}6.7\;mg/dl)$ and had significantly improved glucose tolerance. The overall glucose excursion during the two-hour intraperitoneal glucose tolerance test (IPGTT), calculated as area under the curve (AUC), decreased by $46\%$ (P<0.01) compared to vehicle-treated ob/ob mice. Glucose levels of lean mice were not significantly affected by the extract. The improvement in blood glucose levels in 150 mg/kg extracttreated ob/ob mice was associated with significant reduction in serum insulin levels of fed and fasting mice. Consistent with an improvement in insulin sensitivity, hyperinsulinemic euglycemic clamp study revealed a more than 2-fold increase in the rate of insulin-stimulated glucose disposal in treated ob/ob mice $(112{\pm}19.1\;vs.\;52{\pm}11.8{\mu}mol/kg/min$ for the vehicle group, P<0.01). In addition, 150 mg/kg extract-treated ob/ob mice, but not the lean mice, lost significant weight (from $51.7{\pm}1.9g\;on\;Day\;0\;to\;45.7{\pm}1.2$ on Day 12, P<0.01 compared to vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P<0.05) and a very significant increase in energy expenditure (P<0.01) and body temperature (P<0.01). A 12-day treatment with 150 mg/kg Panax ginseng berry extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re, a major constituent of the ginseng berry, but not from the root, plays a significant role in anti-hyperglycemic action. This anti-diabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism. The identification of a significant anti-hyperglycemic activity in ginsenoside Re may provide an opportunity to develop a novel class of anti-diabetic agent.