Zheng Tao, Yang Xiaoyan, Wu Dan, Xing Shasha, Bian Fang, Li Wenjing, Chi Jiangyang, Bai Xiangli, Wu Guangjie, Chen Xiaoqian, Zhang Yonghui, Jin Si
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
The Key Laboratory of Natural Medicinal Chemistry, Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China.
Br J Pharmacol. 2015 Jul;172(13):3284-301. doi: 10.1111/bph.13120. Epub 2015 Apr 24.
Recent reports have suggested that salidroside could protect cardiomyocytes from oxidative injury and stimulate glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase (AMPK). The aim of this study was to evaluate the therapeutic effects of salidroside on diabetic mice and to explore the underlying mechanisms.
The therapeutic effects of salidroside on type 2 diabetes were investigated. Increasing doses of salidroside (25, 50 and 100 mg·kg(-1) ·day(-1)) were administered p.o. to db/db mice for 8 weeks. Biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of salidroside. Primary cultured mouse hepatocytes were used to further explore the underlying mechanisms in vitro.
Salidroside dramatically reduced blood glucose and serum insulin levels and alleviated insulin resistance. Hypolipidaemic effects and amelioration of liver steatosis were observed after salidroside administration. In vitro, salidroside dose-dependently induced an increase in the phosphorylations of AMPK and PI3K/Akt, as well as glycogen synthase kinase 3β (GSK3β) in hepatocytes. Furthermore, salidroside-stimulated AMPK activation was found to suppress the expression of PEPCK and glucose-6-phosphatase. Salidroside-induced AMPK activation also resulted in phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory chain complex I and disturbed oxidation/phosphorylation coupling and moderately depolarized the mitochondrial membrane potential, resulting in a transient increase in the AMP/ATP ratio.
Salidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria-related AMPK/PI3K/Akt/GSK3β pathway.
近期报道表明，红景天苷可通过激活腺苷酸活化蛋白激酶（AMPK）保护心肌细胞免受氧化损伤，并刺激骨骼肌细胞摄取葡萄糖。本研究旨在评估红景天苷对糖尿病小鼠的治疗效果，并探讨其潜在机制。
研究红景天苷对2型糖尿病的治疗效果。将递增剂量的红景天苷（25、50和100mg·kg⁻¹·天⁻¹）经口给予db/db小鼠，持续8周。进行生化分析和组织病理学检查以评估红景天苷的治疗效果。使用原代培养的小鼠肝细胞在体外进一步探究潜在机制。
红景天苷显著降低血糖和血清胰岛素水平，减轻胰岛素抵抗。给予红景天苷后观察到降血脂作用及肝脂肪变性改善。在体外，红景天苷剂量依赖性地诱导肝细胞中AMPK、PI3K/Akt以及糖原合酶激酶3β（GSK3β）磷酸化增加。此外，发现红景天苷刺激的AMPK活化可抑制磷酸烯醇式丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶的表达。红景天苷诱导的AMPK活化还导致乙酰辅酶A羧化酶磷酸化，这可减少外周组织中的脂质积累。在分离的线粒体中，红景天苷抑制呼吸链复合体I，扰乱氧化/磷酸化偶联，并使线粒体膜电位适度去极化，导致AMP/ATP比值短暂升高。
红景天苷通过激活与线粒体相关的AMPK/PI3K/Akt/GSK3β途径改善细胞代谢通量，从而发挥抗糖尿病作用。
