Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on Type 2 diabetes mice induced by high-fat diet combining with streptozotocin via suppression of hepatic gluconeogenesis

Fitoterapia. 2012 Jan;83(1):192-8. doi: 10.1016/j.fitote.2011.10.011. Epub 2011 Oct 25.


Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type ginsenosides (PDG) from Panax ginseng. Although anti-diabetic activity of CK have been reported with genetic mouse models (db/db mice) in recent years, the therapeutic usefulness of CK and PDG in type 2 diabetes, a more prevalent form of diabetes, remains unclear. In the present investigation, we developed a mouse of non-insulin-dependent diabetes mellitus that closely simulated the metabolic abnormalities of the human disease. For this purpose, type 2 diabetes was induced in male ICR mice by combining of streptozotocin. The male ICR mice fed with HFD for 4 weeks received 100mg/kg of STZ injected intraperitoneally. After 4 weeks, mice with fasting (12h) blood glucose levels (FBG) above 7.8 mmol/L were divided into 3 groups (n=12) and treated with vehicle (diabetes model, DM), 300 mg/kg/day of PDG and 30 mg/kg/day of CK for 4 weeks while continuing on the high-fat diet. Hypoglycemic effects of CK and PDG were consistently demonstrated by FBG levels, and insulin-sensitizing effects were seen during oral glucose tolerance testing (OGTT). Moreover, the mechanism of hypoglycemic effect in type 2 diabetic mice was examined. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in two treatment groups with CK showing greater effects. These findings demonstrated the hypoglycemic and insulin-sensitizing capabilities of CK on type 2 diabetes induced by HFD/STZ via down-regulation of PEPCK and G6Pase expression in liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dietary Fats / adverse effects*
  • Ginsenosides / administration & dosage
  • Ginsenosides / therapeutic use*
  • Gluconeogenesis / drug effects*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Liver / drug effects*
  • Liver / metabolism
  • Mice
  • Molecular Structure


  • Blood Glucose
  • Dietary Fats
  • Ginsenosides
  • Hypoglycemic Agents
  • Insulin
  • ginsenoside M1