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Br J Pharmacol. 2015 Jul;172(13):3284-301. doi: 10.1111/bph.13120. Epub 2015 Apr 24.

Salidroside ameliorates insulin resistance through activation of a mitochondria-associated AMPK/PI3K/Akt/GSK3β pathway.

Zheng T1,2, Yang X1,2, Wu D1,2, Xing S1,2, Bian F1,2, Li W1,2, Chi J1,2, Bai X1,2, Wu G1,2, Chen X1,2, Zhang Y1,2, Jin S1,2,3.

Author information

1
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
2
The Key Laboratory of Natural Medicinal Chemistry, Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China.
3
Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

BACKGROUND AND PURPOSE:

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.

EXPERIMENTAL APPROACH:

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.

KEY RESULTS:

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.

CONCLUSIONS AND IMPLICATIONS:

Salidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria-related AMPK/PI3K/Akt/GSK3β pathway.

PMID:
25754463
PMCID:
PMC4500366
DOI:
10.1111/bph.13120
[Indexed for MEDLINE]
Free PMC Article

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