Comprehensive chemical analysis of Zhenshu Tiaozhi formula and its effect on ameliorating glucolipid metabolic disorders in diabetic rats.

The present study aims to reveal the compositions of Zhenshu TiaoZhi formula (FTZ) comprehensively, and investigate whether FTZ ameliorate glucolipid metabolism disorders in diabetic rats with the involvement of glucocorticoids in peripheral insulin-sensitive tissues. The fingerprint was established based on 11 batches of FTZ samples and chemical compostions of FTZ were identified by ultra performance liquid chromatography-time of flight/mass spectrometry (UPLC-TOF/MS). High-fat diet (HFD) and streptozotocin (STZ) induced diabetic rats were orally administrated with 3 and 6 g/kg body weight of FTZ for 8 weeks. Indices of glucolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI) and blood lipids were evaluated after treatment of FTZ. The levels of HPA axis hormones were examined. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to investigate the relative mRNA expressions of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and glucolipid metabolic indicators. A reference fingerprint was established and 93 compounds of FTZ were tentatively identified. In vivo, FTZ treatment exerted antidiabetic and antidyslipidemic effects while decreased the level of corticotropin releasing hormone (CRH). 11β-HSD1 mRNA showed similar trajectory in both liver, adipose and skeletal muscle tissues, which was up-regulated in diabetic group and ameliorated in FTZ groups. Furthermore, the expressions of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and adipose triglyceride lipase (ATGL) were down-regulated in liver and skeletal muscle. These results elucidated the compositions of FTZ comprehensively and indicated its effect on ameliorating glucolipid metabolism of diabetic rats involved hypothalamus-pituitary-adrenal (HPA) axis homeostasis. Down-regulating 11β-HSD1 in insulin-sensitive tissues might be a potential mechanism of FTZ in treating type 2 diabetes mellitus (T2DM).