Mechanism of Momordica charantia Extract in Regulating Gluconeogenesis in ZDF Diabetes Rats / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo observe the effect of Momordica charantia extract （MCE） on the gluconeogenesis signaling pathway in diabetes rats. MethodMale Zucker Diabetic Fatty （ZDF） rats aged 5-6 weeks were randomly divided into a model group and an MCE group （administered MCE at a dose of 0.40 g·kg-1 by gavage）. Additionally， seven healthy male ZDF （fa/+） rats were assigned to the normal group and received administration once daily for six consecutive weeks. During the experiment， the general condition of the rats was observed， and body weight was recorded. Fasting blood glucose and random blood glucose levels were measured in the 1st， 3rd， and 5th weeks. In the 6th week， an oral glucose tolerance test （OGTT） was conducted， and serum levels of triglycerides （TG）， free fatty acid （FFA）， total cholesterol （TC）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） were measured. Hematoxylin-eosin （HE） staining was performed to examine liver morphology， periodic acid-Schiff （PAS） staining was used to assess hepatic glycogen storage， and Real-time polymerase chain reaction （PCR） was employed to measure the mRNA expression of phosphoenolpyruvate carboxykinase （PEPCK） and glucose-6-phosphatase （G6Pase） in the liver. Western blot analysis was conducted to measure the phosphorylation level of forkhead box protein O1 （FoxO1） and the protein expression of PEPCK and G6Pase in the liver. ResultCompared with the model group， the MCE group showed significant improvements in body weight， fasting blood glucose， random blood glucose， and glucose tolerance （P<0.05， P<0.01） and reduced serum levels of FFA， TC， and TG （P<0.05， P<0.01）. There were no significant differences in ALT and AST between the two groups. In the MCE group， the HE staining revealed more orderly liver cell arrangement and reduced hepatic steatosis and the PAS staining showed increased hepatic glycogen storage. The protein expression of p-FoxO1 in the liver was significantly elevated （P<0.01）， while there was no significant difference in FoxO1 protein expression. The mRNA and protein expression of PEPCK and G6Pase significantly decreased （P<0.05）. ConclusionMCE exhibits glucose-lowering and lipid-lowering effects， improves glucose tolerance， and enhances hepatic glycogen storage. These effects may be attributed to the upregulation of p-FoxO1， leading to the inhibition of PEPCK and G6Pase expression and the regulation of gluconeogenesis-related processes.