Effects of Hydroxysafflor Yellow A on the PI3K/AKT Pathway and Apoptosis of Pancreatic β-Cells in Type 2 Diabetes Mellitus Rats
Effects of Hydroxysafflor Yellow A on the PI3K/AKT Pathway and Apoptosis of Pancreatic β-Cells in Type 2 Diabetes Mellitus Rats
复制标题
羟基红花黄色素A对2型糖尿病大鼠PI3K/AKT通路及胰岛β细胞凋亡的影响
DOI：
10.2147/dmso.s246381
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Liu, Deliang
中科院分区：
文献类型：
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作者：
Lee, Maosheng;Li, Huilin;Liu, Deliang
背景和目的：2型糖尿病（T2 DM）是一种复杂的代谢性疾病，已成为全球主要的公共卫生问题。羟基红花黄色素A（HSYA）是红花的主要活性成分。（红花），在我国广泛用于心脑血管疾病患者。本研究旨在探讨HSYA对高脂饮食（HFD）和链脲佐菌素（STZ-）诱导的T2 DM大鼠的降糖作用及其可能机制。T2 DM大鼠分别给予HSYA（120 mg/kg）或二甲双胍（90 mg/kg）治疗8周。结果：HSYA能显著降低T2 DM大鼠的空腹血糖、口服葡萄糖耐量试验、空腹胰岛素水平和胰岛组织学改变，并能显著降低胰岛素抵抗。Western blot结果显示HSYA逆转了肝脏PI 3 K和AKT的下调。胰腺组织TUNEL法分析表明，HSYA能在一定程度上抑制胰腺β细胞凋亡。此外，HSYA治疗增加了糖原合成酶和肝糖原的水平，并通过降低甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平来改善脂质代谢，尽管它没有改变大鼠的体重。本研究结果提示HSYA可直接或间接促进PI 3 K/Akt活化，抑制胰腺β细胞凋亡，这可能是HSYA改善胰岛素抵抗、调节糖脂代谢的机制之一。
Background and Aim: Type 2 diabetes mellitus (T2DM), a complex metabolic disease, has become a major public health issue around the world. Hydroxysafflor yellow A (HSYA) is the major active chemical ingredient of Carthamus tinctorius L. (safflower), which is widely used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the anti-diabetic effect and potential mechanism of HSYA on the high-fat diet (HFD) and streptozotocin (STZ-)-induced T2DM rats.Materials and Methods: T2DM rats were induced by feeding HFD (60% fat) for four weeks followed by intraperitoneal injection of a low dose of streptozocin (35mg/kg). The T2DM rats were treated with HSYA (120mg/kg) or metformin (90mg/kg) for eight weeks. Biochemical analysis, histological analysis and Western blot analysis were conducted after 8 weeks of intervention.Results: The treatment with HSYA evidently reduced fasting-blood glucose and insulin resistance in T2DM rats, indicated by results from fasting-blood glucose, oral glucose tolerance test, fasting insulin levels and histology of pancreas islets. The Western blot results revealed that HSYA reversed the down-regulation of PI3K and AKT in liver. The TUNEL assay analysis of pancreatic tissue showed that HSYA could inhibit the apoptosis of pancreatic beta-cells to a certain extent. Moreover, HSYA-treatment increased the levels of glycogen synthase and hepatic glycogen and improved lipid metabolism by reducing the triglyceride, total and low-density lipoprotein cholesterol levels, even though it did not change the rats' body weights.Conclusion: The results of this study suggested that HSYA could promote PI3K/Akt activation and inhibit the apoptosis of pancreatic beta-cells directly or indirectly, which might be the underlying mechanisms in HSYA to improve insulin resistance and regulate glycolipid metabolism in T2DM rats.