Effects Of Averrhoa Carambola L. Root Total Extract On Hepatic Glucose Metabolism And Its Protection On Liver In Diabetic Mice

Objective To investigate the effects of Averrhoa carambola L. root total extract(YTG) on hepatic glucose metabolism and its protection on liver in diabetic mice induced by streptozotocin (STZ).Methods Diabetic model was induced by intravenous injection of STZ. Mice were divided into normal group, model group, metformin group, high-, medium-, and low-dose (1.2,0.6,0.3g-kg-1·d-1) of Averrhoa carambola L. root total extract group. Drugs were administered to mice once everyday for 4 weeks.(1) Effects of hepatic glucose metabolism:Observe and record the change of the weight in mice every week. Fasting blood glucose was determined at the 2nd and 4th week. After 4 weeks, oral glucose tolerance test (OGTT), liver glycogen, activities of hexokinase (HK) and pyruvate kinase (PK) were measured. The mRNA expression levels of Glucose-6-phosphatase(G6pase), Phosphoenolpyruvate carboxykinase(PECK) and glycogen synthase kinase-3(3(GSK-3β) were detected by Fluorescence quantitative PCR.(2) The protection of liver:At the end of expriment, Aspartate Transaminase(AST), Alanine transaminase(ALT) and alkaline phosphatase(ALP) in serum were determined by automatic biochemistry analyzer. Take part of the liver tissue to homogenate, tumor necrosis factor alpha (TNF-a) and Interleukin-6 (IL-6) were determined by ELISA, Malondialdehyde(MDA) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px) were tested by colorimetry. The pathological changes of liver tissue were observed by HE.Results (1) Effects of hepatic glucose metabolism:Compared with the model group, the mices’weight of metformin group, YTG high dose and medium dose group were increased significantly (P<0.05 or P<0.01). Compared with the model group, after two weeks of administration, the metformin group, YTG high dose and medium dose group, has obvious hypoglycemic effect, after 4 weeks of administration in each group, fasting blood glucose significantly decreased (P<0.05 or P<0.01). Compared with the model group, the blood glucose area under the curve were reduced significantly in each group (P<0.01). Compared with the model group, the liver glycogen content and the activity of PK in each group was increased significantly, (P<0.05 or P<0.01). The activity of HK in the metformin group and YTG high and middle dose group was enhanced (P<0.05 or P<0.01), the activity of HK in YTG low dose group was increased, but there was no significant difference in statistics. Compared with model group, the relative expression of G6pase in metformin group and YTG high dose and middle dose group was decreased significantly (P<0.05 or P<0.01).The relative expression of PECK in metformin group and YTG high dose group was reduced (P<0.05 or P<0.01). The relative expression of GSK-3β in each group was increased in different degrees, but there was no statistical difference.(2)The protective effects of liver:After 4 weeks of administration, compared with the model group, serum AST, ALT, ALP of each group were significantly decreased (P<0.05, P<0.01). Compared with the model group, the content of TNF-α in each group was decreased significantly in liver (P<0.05, P<0.01). Compared with the model group, the content of IL-6 in metformin group and YTG high, medium dose group were significantly reduced in liver(P<0.01), the content of IL-6 in YTG low dose group was reduced, but there was no significant difference. Compared with model group, the activity of SOD in metformin group and YTG high, medium dose group were increased(P<0.05 or P<0.01), YTG low dose group was increased, but there was no statistically significant difference. The content of MDA in each group was decreased (P<0.05 or P<0.01). Each group of liver GSH-px activities increased significantly (P<0.05 or P<0.01). the pathological examination revealed that YTG had protective effects against the liver injury induced by diabetes.Conclusions YTG through enhance the activity of glucose metabolism enzymes HK, PK and increase the liver glycogen synthesis to reduce the blood glucose levels of diabetic mice, and improve the glucose tolerance; YTG also can decrease the mRNA expression level of the key enzymes of gluconeogenesis G6pase and PECK, hepatic gluconeogenesis and glucose output were decreased There is a protective effect on liver injury induced by diabetes, its mechanism may be related to the reduction in hepatic inflammation factor of production and enhance the activity of antioxidant enzymes in the liver.