Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.
Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.
Biomed Pharmacother. 2021 Jan;133:111060. doi: 10.1016/j.biopha.2020.111060. Epub 2020 Dec 8.
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).
本研究旨在全面揭示真武调脂方（FTZ）的组成，并探讨 FTZ 是否通过外周胰岛素敏感组织中的糖皮质激素改善糖尿病大鼠的糖脂代谢紊乱。基于 11 批 FTZ 样品建立了指纹图谱，并通过超高效液相色谱-飞行时间/质谱联用（UPLC-TOF/MS）鉴定了 FTZ 的化学成分。采用高脂饮食（HFD）和链脲佐菌素（STZ）诱导糖尿病大鼠，分别给予 FTZ 3 和 6 g/kg 体重，连续灌胃 8 周。FTZ 治疗后评估糖脂代谢指标，包括空腹血糖（FBG）、空腹胰岛素、胰岛素抵抗指数（IRI）和血脂。检测 HPA 轴激素水平。采用逆转录-聚合酶链反应（RT-PCR）检测 11β-羟类固醇脱氢酶 1（11β-HSD1）和糖脂代谢相关指标的相对 mRNA 表达。建立参考指纹图谱，初步鉴定 FTZ 中的 93 种化合物。体内，FTZ 治疗具有降血糖和降血脂作用，同时降低促肾上腺皮质激素释放激素（CRH）水平。11β-HSD1 mRNA 在肝脏、脂肪和骨骼肌组织中表现出相似的变化趋势，在糖尿病组中上调，在 FTZ 组中改善。此外，肝脏和骨骼肌中葡萄糖-6-磷酸酶（G6Pase）、磷酸烯醇丙酮酸羧激酶（PEPCK）和脂肪甘油三酯脂肪酶（ATGL）的表达下调。这些结果全面阐明了 FTZ 的组成，并表明其改善糖尿病大鼠糖脂代谢的作用涉及下丘脑-垂体-肾上腺（HPA）轴的稳态。下调胰岛素敏感组织中的 11β-HSD1 可能是 FTZ 治疗 2 型糖尿病（T2DM）的潜在机制。
