Effects Of Traditional Chinese Medicine Sutherlandia Frutescens On Glucose And Lipid Metabolism In Mice And Its Mechanism

ObjectivesSutherlandia frutescens frutescens has been marked as a potential hypoglycaemic agent for the treatmentof type 2 diabetes. In this study, we investigated the effects and mechanism of a aqueous extract of Sutherlandia frutescens from South African traditional medicines on type 2 diabetes in a diabetic KKAy mouse model and C57BL/6J mouse model. It hoped that the study will enrich the scientific connotation of the role of diabetes, lay a good foundation for the development of new diabetes drugs, and provide experimental basis for clinical use natural medicines.MethodsStudy 1,2 and 3 investigated the effects and potential mechanism of Sutherlandia frutescens frutescens in spontaneous KKAy diabetes mice and normal C57BL/6J mice. KKAy diabetes mice were randomly divided into model group, Sutherlandia frutescens low, medium and high dose extract group, and Metformin group. C57BL/6J mice were randomly divided into normal group and normal high dose group which is treated by Sutherlandia frutescens high dose extract. Mice was orally administered 7 weeks.It was recorded the body weight, food and drinking intake of experimental mice Weekly, and every two weeks tested mice fasting blood glucose and serum lipid. At the time of 35d and 42d, mice were fasted 4h for ITT and OGTT. Mice were executed after orally administered 7 weeks, Reserved the serum and tissue. Various physiological parameters were measured. We used utomatic biochemical analyzer test blood lipid (TG, TC, HDL-C, LDL-C), liver function and renal function, ELISA method determination of serum insulin levels, the kits determination of liver tissue oxidative stress indicators (MDA, SOD and GR), enzymatic methods determination of TG and TC content in liver tissue, HE dyeing observation in mice liver morphological changes, PAS staining observation in the mice liver glycogen reserve, Real-time quantitative PCR detection gene expression level of insulin signaling pathway related of IR, IRS-1, PI3K, AKT-1, GSK-3β, GLUT4, and liver lipid synthesis metabolism related indexes (SREBP-1c, FAS, HMG-CoA, UCP2, CPT-1, HSL, PPAR a), Western blot detection protein expression levels of P-AKT (Ser473) and GSK-3β.ResultsThe Study 1 results show that as follows. Sutherlandia frutescens extract can slow down the weight gain rate for obesity mice without affect eating and drinking, in that the low dose displayed best. In comparison to KKAy mice fed high fat diet only (positive control for T2DM), levels of fast blood glucose, serum lipids of TG, TC and LDL-C were significantly reduced during treatment of Sutherlandia frutescens extract 7weeks, and levels of serum HDL-C were significantly elevated.middle and high dose displayed best. While Sutherlandia frutescens extract did not affected these indexes in normal C57BL/6J mice gavaged with Sutherlandia frutescens high dose extract. Low dose of Sutherlandia frutescens also play a fine performance to increase insulin sensitivity and improve glucose tolerance abnormalities in ITT and OGTT test comparison to model group. Sutherlandia frutescens extract Reduced the liver transaminase playing a role of protecting the liver. Besides, it has not been found liver and kidney toxicity of Sutherlandia frutescens extract.The Study 2 results show that the low dose of Sutherlandia frutescens stimulated the expression of P-AKT Ser473, and inhibit the expression of GSK-3β. At the same time, Sutherlandia frutescens can up-regulated gene expression of InsR, IRS-1, PI3K, AKT-1, GLUT4, and down-regulated gene expression of GSK-3 β. That means that the low dose of Sutherlandia frutescens play the role in activation of insulin signal transduction pathways, in order to increase glucose uptake and promote the liver glycogen synthesis.The Study 3 results show that as follows. First of all, Sutherlandia frutescens can decrease liver cell vacuoles degeneration, and significantly reduce the liver triglyceride and total cholesterol levels, improve fatty liver of KKAy mice due to accumulation of excess fatty. Secondly, Sutherlandia frutescens can decrease the MDA level in liver tissue, increase SOD and GR levels, and improve the oxidative stress state of KKAy mice. Thirdly, Sutherlandia frutescens suppressed the gene expression of SREBP-1c, FAS, HMG-COA in the liver, so as to inhibit of fatty acid from scratch, and the synthesis of cholesterol, for effect of reducing triglyceride and cholesterol in the liver. Fourthly, Sutherlandia frutescens inhibited HSL gene expression, resulting in suppressed adipose decompose. Lastly, we test the gene expression of CPT-1, PPAR a in the liver, but not obtain the function.ConclusionSutherlandia frutescens extracts of South Africa’s traditional herb can improve gluco-lipid metabolism, improve the insulin resistance, protecting the liver and kidney without side effects so far in T2DM animal model. Meanwhile there is no effect on gluco-lipid metabolism of normal mice. The effect may be achieved by the following pathway:(1) By regulating hepatic insulin PI3K/Akt/GSK-3 beta signaling pathways and PI3K/Akt/GLUT4 signaling pathways, increase the liver to glucose uptake and promote the liver glycogen synthesis, so as to improve insulin resistance and lower blood sugar levels in the body, low-dose of Sutherlandia frutescens mainly through this mechanism and regulate gluco-lipid metabolism. (2) By regulating key factor from lipid scratch, lipolysis, energy metabolism so as to improve liver lipid metabolism disorders. (3) By improve the oxidation resistance to inhibit oxidative stress in the body.