Effects of artemether on glucose and lipid metabolism in C57BL/KsJ-db/db mice / 中草药

ABSTRACT

Objective To investigate the effects of different doses of artemether on glycolipid metabolism in C57BL/KsJ-db/db mice. Methods Eight-week-old male C57BL/KsJ-db/db mice were divided into model group (ig given 1% methylcellulose) and artemether 400, 200, 100, 50 groups (ig given 400, 200, 100, 50 mg/kg artemether respectively + 1% methylcellulose), with six mice in each group. Another six male C57BL/KsJ-db/+ mice were selected as the control group. All groups were administered for 4 weeks. The quality of the mice was measured every 2 d; The food intake of the mice was measured every 3 d and the average daily food intake and body mass changes were evaluated; The amount of water in mice was measured every 2 d; The urine volume of the mice was measured every 3 d; After 8 h of fasting, blood was collected from the tail vein, and the fasting blood glucose of the mice was measured by Roche blood glucose meter and matching test paper every 7 d. Mice were assessed for glucose tolerance and sensitivity to insulin by ip glucose tolerance test (IPGTT) and ip insulin tolerance test (IPITT). The serum total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) levels of the mice were determined by a biochemical kit. The whole liver of mice was weighed and the morphological changes of the pancreas and liver in mice were observed by HE staining. The expression of AMP-activated protein kinase (AMPK), glucose transporter 4 (GLUT-4), and insulin receptor β (IRβ) protein in liver of mice was analyzed by Western blotting. Results Compared with the control group, the food intake, water intake, and urine volume of the model group were significantly increased (P < 0.001). Compared with the model group, each dose of artemether significantly reduced the water intake and urine volume of the mice (P < 0.01, 0.001); Artemether 400, 200, 100 mg/kg can significantly reduce the body weight and food intake in a dose-dependent manner (P < 0.05, 0.01); Artemether 400, 200, 100 mg/kg significantly reduced fasting blood glucose levels in mice, reduced the area under the curve of IPGTT (AUCs), and improved insulin resistance in mice (P < 0.01, 0.001). Compared with the control group, the TC, TG, and FFA levels of mice in the model group were significantly increased (P < 0.05). Compared with the model group, artemether significantly decreased the levels of TC, TG, and FFA in the serum of mice in a dose-dependent manner (P < 0.05), and significantly improved islet vacuolar degeneration and hepatic steatosis in db/db mice; The protein expression of AMPK, GLUT-4, and IRβ in the liver of mice was increased (P < 0.05). With the prolongation of the intervention time, the higher the dose of artemether, the higher the mortality rate and the incidence of adverse reactions in mice. Conclusion Artemether can significantly improve the high-fat state and insulin resistance of diabetic mice. It can treat fatty liver and may up-regulate the expression of GLUT-4 and IRβ protein through the AMPK pathway to exert its effects. It is expected to be used in the treatment of type 2 diabetes mellitus, which is mainly caused by metabolic syndrome. However, higher doses of artemether and longer-term application may lead to more adverse events.