Objective

2

To explore the effects of

Banxia Xiexin Decoction

（半夏泻心汤） on gastric emptying in diabetic gastroparesis （DGP） mice and the possible mechanism.

Methods

2

Thirty female db/db spontaneous type 2 diabetic mice were fed with high-fat and high-sugar diet for one week as adaption， and then DGP mice， when the gastric half emptying time （T

1/2

）＞129 min for two consecutive times， were distinguished with non-DGP mice by

13

C caprylic acid breath test. Five non-DGP mice were set as the type 2 diabetes control group， and the DGP mice were randomly divided into the DGP model group， the metoclopramide group， and low-， medium- and high-dose

Banxia Xiexin Decoction

groups， with five mice in each group. All mice were given 250 mg/（kg·d） of metformin. Additionally， 10 mg/（kg·d） of metoclopramide and 750， 1500， and 3000 mg/（kg·d） of

Banxia Xiexin Decoction

were given by gavage to the mice in the metoclopramide group， low-， medium- and high-dose

Banxia Xiexin Decoction

groups， respectively， all for eight consecutive weeks. After eight weeks， fasting blood glucose was tested， and intraperitoneal glucose tolerance test was performed. The area under the glucose tolerance curve was used to evaluate glucose sensitivity in mice. T

1/2

was calculated using the

13

C breath test to assess gastric motility. The number of interstitial cells of Cajal （ICCs） and their stem cells （ICC-SC）， the content of advanced glycation end products （AGEs）， and the expression levels of receptor for advanced glycation endproducts （RAGE） and neuronal nitric oxide synthase （nNOS） in gastric tissue were measured.

Results

2

Compared to those in the type 2 diabetes control group， the fasting blood glucose， the glucose area under the curve， and T

1/2

of the mice in the DGP model group all increased， while the number of ICCs and ICC-SC in gastric tissue significantly decreased； the content of AGEs and RAGE protein expression increased， while the expression of nNOS protein decreased （

P

＜0.01）. Compared to those in the GDP model group and the metoclopramide group， the fasting blood glucose level and the glucose area under the curve of mice in the medium- and high-dose

Banxia Xiexin Decoction

groups were significantly lower， while the number of ICCs and ICC-SC in gastric tissue significantly increased； the content of AGEs and the expression level of RAGE were significantly lower， while the expression level of nNOS was higher （

P

＜0.01）. T

1/2

was shortened in the high-dose

Banxia Xiexin Decoction

group than in the metoclopramide group （

P

＜0.01）. The number of ICCs， ICC-SCs and the expression of nNOS protein in the high-dose

Banxia Xiexin Decoction

group increased， while the content of AGEs decreased compared to those in the medium- and low-dose groups （

P

＜0.01）.

Conclusion

2

Banxia Xiexin Decoction

can improve the level of blood glucose and accelerate gastric emptying in DGP model mice， and the effect is best at high dose. Its molecular mechanism may be related to the inhibition of the production of AGEs and the expression of RAGE， and the up-regulation of the expression of nNOS to regulate the proliferation of ICCs and ICC-SC， thereby enhancing the gastric motility.