Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, BHU, Varanasi 221005, India.
Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, India.
Life Sci. 2019 Nov 1;236:116836. doi: 10.1016/j.lfs.2019.116836. Epub 2019 Sep 4.
The present experiment was conceptualised to explore the therapeutic response of tetramethylpyrazine (TMP), a major active constituent of Ligusticum chuanxiong, a Chinese traditional medicinal plant, in high-fat diet (HFD)-streptozotocin (STZ)-induced diabetes in rats and to identify the possible mechanism of action.
Dose-reliant effect of oral treatment of TMP (100, 150 and 200 mg/kg/day) for 28 days was evaluated by calculating the alteration in body weight, level of fasting blood glucose (FBG), plasma insulin, homeostasis model assessment (HOMA), serum lipids, oral glucose & intraperitoneal insulin tolerance and glycosylated haemoglobin in HFD-STZ-induced type-2 diabetic (T2D) rats and underlying molecular mechanisms of TMP was also studied.
TMP treatment prominently reduced the level of FBG, glycosylated haemoglobin and revived body weight gain and level of serum insulin dose-dependently in diabetic rats. TMP treatment considerably improved insulin resistance, as observed in oral glucose tolerance and insulin tolerance tests. Moreover, dose-dependent reduction in the level of pro-inflammatory cytokines, C-reactive protein (CRP) and interleukin-6 (IL-6) was observed and their level was found to be significantly reduced in highest dose TMP (200 mg/kg) treated diabetic rats, pointing towards TMP mediated recovery of insulin signalling and a decrease in insulin resistance. The expressions of p-PI3K-p85/p-Akt/GLUT-4 were also significantly up-regulated by TMP (200 mg/kg), suggesting the connection of the PI3K/Akt signal pathway in the anti-hyperglycemic action of TMP.
These findings suggest that TMP may be used as a potential agent for type-2 diabetes treatment.
本实验旨在探讨川芎嗪（一种中药川芎的主要活性成分）对高脂肪饮食（HFD）-链脲佐菌素（STZ）诱导的糖尿病大鼠的治疗反应，并确定其可能的作用机制。
通过计算体重变化、空腹血糖（FBG）水平、血浆胰岛素、稳态模型评估（HOMA）、血清脂质、口服葡萄糖和腹腔内胰岛素耐量以及 HFD-STZ 诱导的 2 型糖尿病（T2D）大鼠糖化血红蛋白的变化，评估川芎嗪（100、150 和 200mg/kg/天）口服治疗 28 天的剂量依赖性效应，并研究川芎嗪的潜在作用机制。
川芎嗪治疗可显著降低糖尿病大鼠的 FBG、糖化血红蛋白水平，并显著恢复体重增加和血清胰岛素水平，呈剂量依赖性。川芎嗪治疗可显著改善胰岛素抵抗，表现在口服葡萄糖耐量和胰岛素耐量试验中。此外，还观察到促炎细胞因子、C 反应蛋白（CRP）和白细胞介素-6（IL-6）水平呈剂量依赖性降低，且在最高剂量（200mg/kg）川芎嗪治疗的糖尿病大鼠中其水平显著降低，表明川芎嗪介导的胰岛素信号恢复和胰岛素抵抗降低。TMP（200mg/kg）还显著上调 p-PI3K-p85/p-Akt/GLUT-4 的表达，提示 PI3K/Akt 信号通路与 TMP 的抗高血糖作用有关。
这些发现表明，川芎嗪可能作为 2 型糖尿病治疗的潜在药物。
