Effect and underlying mechanism of Huangjing Qianshi decoction in pre-diabetes mouse model
摘要
Insulin secretion deficiency and increased insulin resistance are key pathological pathways that lead to pre-diabetes. Without intervention, pre-diabetes can easily develop into type 2 diabetes mellitus. However, no specific medicine is available for treating pre-diabetes except for intervention through lifestyle changes. Huangjing Qianshi decoction (HJQST) is a qi-replenishing and yin-nourishing Chinese medicinal compound. However, the mode and mechanism of action of HJQST in improving pre-diabetes remain unclear. Here, we studied the effect of HJQST on pre-diabetes.
MethodsBKS-db mice were induced to develop pre-diabetes and treated with HJQST and metformin (MET). After treatment for 51 days, hematoxylin-eosin and oil red O staining were used to analyze the pathological damage and lipid droplet formation in the pancreatic, liver and skeletal muscle of pre-diabetic mice. Serum levels of free fat acid (FFA), glycated hemoglobin A1c (HbA1c), fasting insulin (INS), reactive oxygen species (ROS), and tumor necrosis factor-α (TNF-α) were analyzed. Levels of glucose transporter 4 (GLUT-4), INS, nuclear receptor subfamily 3 group c member 2 (NR3C2), phosphorylated-signal transducer and activator of transcription 1 (p-STAT1), peroxisome proliferator activated receptor co-activator 1 α (PGC-1α), and protein inhibitor of activated STAT1 (PIAS1) protein were analyzed by immunohistochemistry and western blot.
ResultsThe body weight, fasting blood glucose (FBS) levels, and serum levels of HbA1c, FFA, ROS, and TNF-α were significantly decreased, whereas the insulin level was significantly increased in pre-diabetic BKS-db mice after HJQST treatment. Additionally, HJQST treatment improved pancreatic and liver damage and the lipid droplet formation in liver and skeletal muscle. Furthermore, the increased NR3C2 and p-STAT1 protein levels and decreased GLUT-4, INS, PIAS1, and PGC-1a protein levels in pre-diabetic mice were reversed by HJQST treatment.
ConclusionHJQST treatment could reverse high FBS level and aberrant lipid metabolism, oxidative stress, and inflammation in pre-diabetes, all of which are related to the NR3C2/PIAS1/STAT1/PGC-1α signal axis.