Salvianolic Acid B Ameliorates Hyperglycemia and Dyslipidemia in db/db Mice through the AMPK Pathway

Salvianolic Acid B Ameliorates Hyperglycemia and Dyslipidemia in db/db Mice through the AMPK Pathway
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丹酚酸 B 通过 AMPK 途径改善 db/db 小鼠的高血糖和血脂异常

DOI:
10.1159/000453151
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发表时间:
2016-01-01
影响因子:
--
通讯作者:
Wang, Pei-Jian
Wang, Pei-Jian
中科院分区:
医学1区
文献类型:
--
作者:
Huang, Ming-Qing;Zhou, Cai-Jie;Wang, Pei-Jian

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背景/目的:丹参酚酸B是丹参的主要多酚类化合物,具有潜在的抗糖尿病活性。然而,Salb在2型糖尿病中的作用机制还没有得到广泛的研究。本研究旨在探讨丹参皂苷B对自发性2型糖尿病模型糖尿病相关代谢改变的影响及其可能的分子机制。方法:雄性C57BL/KSJ-db/db小鼠灌胃给予SAL B(50 mg/kg和100 mg/kg)或二甲双胍(阳性药300 mg/kg),连续6周。结果:丹参B能显著降低db/db小鼠的空腹血糖、血清胰岛素、甘油三酯和游离脂肪酸水平,降低肝脏糖异生基因的表达,改善胰岛素耐受。大剂量丹参素B可明显改善糖耐量,增加肝脏糖酵解基因表达和肌糖原含量,改善胰腺组织病理改变,与二甲双胍相似。丹参B可增加骨骼肌和肝脏磷酸化AMP活化蛋白激酶(p-AMPK)蛋白表达,增加骨骼肌葡萄糖转运蛋白4(GLUT4)和糖原合成酶蛋白表达,增加肝脏过氧化物体增殖物激活受体α(PPARα)和磷酸化乙酰辅酶A羧基酶(p-ACC)蛋白表达。结论:我们的数据提示SAL B在预防和治疗2型糖尿病方面显示出有益的作用,至少部分是通过调节AMPK通路。(C)2016年作者(S),S.Karger AG,巴塞尔出版
Background/Aims: Salvianolic acid B (Sal B), a major polyphenolic compound of Salvia miltiorrhiza Bunge, has been shown to possess potential antidiabetic activities. However, the action mechanism of SalB in type 2 diabetes has not been investigated extensively. The present study was designed to investigate the effects of Sal B on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as its potential molecular mechanism. Methods: Male C57BL/KsJ-db/db mice were orally treated with Sal B (50 and 100 mg/kg) or metformin (positive drug, 300 mg/kg) for 6 weeks. Results: Both doses of Sal B significantly decreased fasting blood glucose, serum insulin, triglyceride and free fatty acid levels, reduced hepatic gluconeogenic gene expression and improved insulin intolerance in db/db mice. High dose Sal B also significantly improved glucose intolerance, increased hepatic glycolytic gene expression and muscle glycogen content, and ameliorated histopathological alterations of pancreas, similar to metformin. Sal B treatment resulted in increased phosphorylated AMP-activated protein kinase (p-AMPK) protein expression in skeletal muscle and liver, increased glucose transporter 4 (GLUT4) and glycogen synthase protein expressions in skeletal muscle, and increased peroxisome proliferator-activated receptor alpha (PPAR alpha) and phosphorylated acetyl CoA carboxylase (p-ACC) protein expressions in liver. Conclusion: Our data suggest that Sal B displays beneficial effects in the prevention and treatment of type 2 diabetes at least in part via modulation of the AMPK pathway. (C) 2016 The Author(s) Published by S. Karger AG, Basel