Hypoglycemic Effect Of Chrysanthemum Morifolium Extract And Potential Mechanisms In Mice

Aim: To examine the hypoglycemic effect of Chrysanthemum morifolium extract(CME) and potential mechanisms in mice.Methods: Normal mice were orally given the CME 300 mg/kg for 45 days, and then the fasting blood glucose(FBG) and glucose tolerance test were measured to observe whether the CME has a hypoglycemic effect. The alloxan-induced diabetic mice were randomly divided into four groups: model group, CME 150 and 300 mg/kg groups, and Xiaoke pills 600 mg/kg group. A control group was added additionally. The mice in the medicine-treated groups were given CME or Xiaoke pills by gavage based on different doses for 6 weeks, the food intake and water intake were daily recorded, and the FBG was measured once a week. After administration for 6 weeks, these mice were killed, the blood, liver, and muscle were taken, the FBG, serum superoxide dismutase(SOD) and malondialdehyde(MDA), liver and muscle glycogens were measured with the colorimetric method, the serum insulin level was measured by ELISA, the injury degree of islet cells was determined by immunohistochemical method, the protein expressions of hepatic peroxisome proliferator-activated receptor(PPAR) α, glycogen synthase(GS), and glucose transporter-2(Glut-2) were examined by Western Blot method, respectively. The BRL cells were utilized to observe the effects of CME-rich serum on cultured supernatant glucose content as well as PPARα and GS protein expressions. To further determine whether the hypoglycemic mechanism of CME was associated with the pathway of PPARα,BRL cells were pretreated with PPARα inhibitor MK886 1 μmol/L for 2 h, the change of GS protein expression were then determined.Results: After administration of CME 300 mg/kg for 45 days, the FBG was decreased(P<0.05), while the glucose tolerance at 2h was increased in normal mice(P<0.05). After treatment of diabetic mice with CME 150-300 mg/kg 6 weeks, the FBG level was reduced in different degrees, especially in sixth week(P<0.05),the food intake and water intake were decreased as well(P<0.05 or P<0.01). The serum insulin level was increased in some degree and the partial islet β-cells were recovered from damage. However, the homeostasis model assessment of insulin resistance(HOMA-IR),serum SOD and MDA contents between the model group and medicine-treated groups were not significantly different. CME could increase the content of liver glycogen in diabetic mice, especially the CME 300 mg/kg(P<0.05), but the content of muscle glycogen was not different from that of model group. Western Blot assays showed that CME could up-regulate the liver PPARα, GS and Glut-2 protein expressions(P<0.01 or P<0.05). In vitro, after treatment of BRL cells with CME-rich serum, the glucose content in cultured supernatant was decreased(P<0.05), while PPARα and GS protein expressions in cells were increased(P<0.01).But the effect of CME-rich serum on GS protein expression was decreased after pretreatment with PPARα inhibitor MK886(P<0.05).Conclusion: CME had a hypoglycemic effect in diabetic mice, and its mechanisms might be associated with the recovery of partial damaged islet β-cells and increments of hepatic PPARα, GS, and Glut-2 protein expressions. The former may promote the insulin synthesis and release, and the latter may accelerate the glucose uptake from blood and subsequent synthesis of liver glycogen.