Effect and underlying mechanism of Huangjing Qianshi decoction in pre-diabetes mouse model.

BACKGROUND: 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. METHODS: BKS-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. RESULTS: The 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. CONCLUSION: HJQST 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.