Antiobesity and Antihyperglycemic Effects of Ginsenoside Rb1 in Rats

OBJECTIVE: Obesity and type 2 diabetes are national and worldwide epidemics. Because currently available antiobesity and antidiabetic drugs have limited efficacy and/or safety concerns, identifying new medicinal agents, such as ginsenoside Rb1 (Rb1) as reported here, offers exciting possibilities for future development of successful antiobesity and antidiabetic therapies. RESEARCH DESIGN AND METHODS: Changes in feeding behavior after acute intraperitoneal administration of Rb1 and the effects of intraperitoneal Rb1 for 4 weeks on body weight, energy expenditure, and glucose tolerance in high-fat diet (HFD)-induced obese rats were assessed. We also examined the effects of Rb1 on signaling pathways and neuropeptides in the hypothalamus. RESULTS: Acute intraperitoneal Rb1 dose-dependently suppressed food intake without eliciting signs of toxicity. This inhibitory effect on feeding may be mediated by central mechanisms because Rb1 stimulated c-Fos expression in brain areas involved in energy homeostasis. Consistent with this, Rb1 activated the phosphatidylinositol 3-kinase/Akt signaling pathway and inhibited NPY gene expression in the hypothalamus. Four-week administration of Rb1 significantly reduced food intake, body weight gain, and body fat content and increased energy expenditure in HFD-induced obese rats. Rb1 also significantly decreased fasting blood glucose and improved glucose tolerance, and these effects were greater than those observed in pair-fed rats, suggesting that although Rb1's antihyperglycemic effect is partially attributable to reduced food intake and body weight; there may be additional effects of Rb1 on glucose homeostasis. CONCLUSIONS: These results identify Rb1 as an antiobesity and antihyperglycemic agent.