Objective: To investigate the hypoglycemic effect of different proportions of Coptidis Rhizoma and Cinnamonin Cortex (10:1

10:3

10:6) in Jiaotai pill and relevant mechanisms. Method: The 12-weeks-old db/db mice were randomly divided into Coptidis Rhizoma and Cinnamonin Cortex groups (with the proportions of 10:1

10:3

10:6

equal to 8.4

10

12.3 g·kg-1 of crude drug)

positive drug group (metformin

0.25 g·kg-1) and the model group. Other db/m mice of the same age were selected into the normal group. The normal group and the model group were given saline solution

intragastric administration

the positive drug group was given metformin suspension

intragastric administration

while the Jiaotai pill groups with different proportions were given the corresponding water decoction

intragastric administration

once a day. After 5 weeks

body weight

food and water intake

and fasting blood glucose (FBG) were measured. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were performed. The changes in pancreas islet β cells morphology and ultrastructure were analyzed by immunohistochemistry and under transmission electron microscopy. Western blot was used to analyze the expressions of adenosine 5'-monophosphate-activated protein kinase (AMPK)

phosphorylated AMPK in liver

white adipose tissue and skeletal muscle

as well as the expression of glucose transporter 4 (GLUT4) in white adipose tissue and skeletal muscle. Result: Compared with the normal group

the db/db mice showed increases in body weight

water and food intake

high fasting blood glucose (P<0.01). IPGTT and IPITT at each time point increased (P<0.01). The numbers of islet β cells and granules in β cells decreased in db/db mice. The expression of phosphorylated AMPK in liver

white adipose tissue and skeleton muscle were lower (P<0.05)

and the expression of GLUT4 in adipose tissue and muscle were decreased in db/db mice (P < 0.05

P < 0.01). Compared with the model group

FBG of the three Rhizoma coptidis and cinnamon groups with different proportions were significantly lower (P<0.05)

IPGTT and IPITT were alleviated

the numbers of pancreas islet β cells and granules in β cells were higher than the model group. Among three groups

the effect of Rhizoma coptidis and cinnamon with the proportion of 10:1 was the most obvious. The expression of phosphorylated AMPK was increased in the liver

adipose tissue and muscle of db/db mice treated with Jiaotai pill 10:1 group (P<0.05). And the expression of GLUT4 was also increased in adipose tissue and muscle of Jiaotai pill 10:1 group (P < 0.05

P < 0.01). Conclusion: Jiaotai pill composed of Rhizoma coptidis and cinnamon with different proportions has a certain effect in decreasing blood glucose

and that with the proportion of 10:1 showed the best effect. Its mechanism is related to activation of AMPK and increase in the expression of GLUT4.