MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model

Ethnopharmacological relevance: Ophiopogon japonicus is a traditional Chinese medicine that might be helpful for the treatment of type 2 diabetes. Recent studies have confirmed its beneficial properties, but not the mechanism of action. Aim of study: In this study, we examined the effects of a water-soluble beta-D-fructan (MDG-1) from O. japonicus on type 2 diabetes through the PI3K/Akt pathway in a diabetic KKAy mouse model. Materials and methods: MDG-1 was extracted from the tube root of O. japonicus and purified as described previously (Xu et al., 2005). The KKAy mice were gavaged once daily with either distilled water. MDG-1or rosiglitazonefor 8 weeks. Blood glucose levels were tested regularly for the fed and fasted mice. In order to evaluate the effect of MDG-1 on disease progression, the proteins of InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 were detected by Western blotting and serum TG, TC, HDL-C, LDL-C were also dertermined. Results: MDG-1 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia in the KKAy mice. The oral glucose tolerance test (OGTT) and the level of insulin in the serun showed that insulin resistance in KKAy mice was ameliorated after MDG-1 treated. After 8 weeks treatment with 300 mg/kg MDG-1, the content of triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) the serum decreased significantly. Meanwhile high density lipoprotein cholesterol (HDL-C) content increased notably. MDG-1 did not have any effect on total cholesterol (TC) content in the serum, whereas rosiglitazone significantly decreased the TC content. In addition, MDG-1 upregulates the phosphoinositide 3-kinase p85 subunit, Akt, insulin receptor (InsR), insulin receptor substrate-1 (IRS-1) and Glut-4 expression, but downregulates glycogen synthase kinase 3 beta expression. Conclusions: These data indicate that MDG-1 has remarkable anti-diabetic activity through the InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 signaling pathway. We believe that MDG-1 is a promising anti-diabetic compound that will be helpful for the treatment of T2DM. (c) 2012 Elsevier Ireland Ltd. All rights reserved.