Anti-diabetic Effects Of Tuberous Root Of Liriope Spicata Var. Prolifera On Stz-induced Type 2 Diabetic Mice And Its Probable Mechanisms

Objective: The present study was designed to investigate the anti-diabetic effects of the tuberous root of Liriope spicata (Thunb.) var. prolifera Y. T. Ma on STZ-induced type 2 diabetic mice and its probable anti-diabetic mechanisms.Method: Based on the study of the extraction and separation of polysaccharides from Liriope spicata (Thunb.) var. prolifera, the water extract (WE), the crude polysaccharides (CPs), the water eluting fraction (DEAE-1) and the salt solution eluting fraction (DEAE-2) of DEAE-cellulose 52 column were obtained. These 4 fractions were administered orally at different doses (200 and 100mg/kg body weight) to normal and streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice, respectively. The active fractions from WE, CPs, DEAE-1 and DEAE-2 were selected through the results of fasting blood glucose (FBG). The oral glucose tolerance test (OGTT) was performed, and the fasting serum insulin (FINS) as well as lipid levels were estimated for the evaluation of the anti-diabetic effects of Liriope spicata (Thunb.) var. prolifera. After 4 weeks of administration, immunohistochemistry and western blot were applied to detect the expression levels of insulin receptor-α(InsR-α), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) in renal tissues of mice. Moreover, the hepatic glycogen content, glucokinase (GK) and glucose-6-phosphatase (G6Pase) activities were measured to investigate the effects of WE and CPs on glucose metabolism.Results: Doses of WE, CPs, DEAE-1and DEAE-2 did not show any appreciable effects on FBG in normal mice. However, WE, CPs and DEAE-1, which were served as the active fractions, caused a marked decrease of FBG, yet DEAE-2 showed no hypoglycemic activities. WE, CPs and DEAE-1 had a significant improvement on glucose tolerance and insulin resistance in STZ-induced type 2 diabetic mice. In addition, while lowering total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL) levels, WE, CPs and DEAE-1 elevated the relative high density lipoprotein cholesterol (HDL/TC) level in serum. The analysis of immunohistochemistry and western blot showed: compared with diabetic control, greater immunostaining for InsR-α, IRS-1 and PI3K was present in the tubulointerstitial regions of WE, CPS and DEAE-1 groups and the expression levels of these three signal molecules were significantly increased in renal tissues; the glycogen content and GK activity from WE, CPS and DEAE-1 groups in liver were significantly increased, yet the G6Pase activity was significantly lower.Conclusion: The hypoglycemic ingredients of Liriope spicata (Thunb.) var. prolifera are polysaccharides, which show the activities of improving hyperglucemia, hyperlipidemia, hyperinsulinemia and insulin resistance. One of the anti-diabetic mechanisms may be related with the amelioration of insulin signaling transduction and glucose metabolism.