Gastrodin attenuation of the inflammatory response in H9c2 cardiomyocytes involves inhibition of NF-κB and MAPKs activation via the phosphatidylinositol 3-kinase signaling

被引：165

作者：

Yang, Ping ^{[1
]}

Han, Yi ^{[2
]}

Gui, Li ^{[3
]}

Sun, Jun ^{[1
]}

Chen, Yuan-li ^{[1
]}

Song, Rui ^{[4
]}

Guo, Jia-zhi ^{[1
]}

Xie, Ya-nan ^{[1
]}

Lu, Di ^{[1
]}

Sun, Lin ^{[4
]}

机构：

[1] Kunming Med Univ, Fac Basic Med Sci, Dept Anat, Chenggong Dist 650500, Kunming, Peoples R China

[2] Kunming Med Univ, Fac Basic Med Sci, Dept Physiol, Chenggong Dist 650500, Kunming, Peoples R China

[3] Third Peoples Hosp Yunnan Prov, Dept Endocrinol, Kunming 650011, Peoples R China

[4] Kunming Med Univ, Affiliated Hosp 2, Dept Cardiol, Chenggong Dist 650500, Kunming, Peoples R China

来源：

BIOCHEMICAL PHARMACOLOGY | 2013年 / 85卷 / 08期

关键词：

Gastrodin; Inflammatory response; NF-kappa B; PI3-K/Akt; H9c2; cardiomyocytes; INDUCED MYOCARDIAL DYSFUNCTION; CARDIAC-SPECIFIC EXPRESSION; IN-VIVO; PATHWAY; SEPSIS; MICE; MECHANISM; CELLS; ENDOTOXEMIA; MORTALITY;

D O I：

10.1016/j.bcp.2013.01.020

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

The phenolic glucoside gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties. However, the role and precise molecular mechanisms explaining how gastrodin suppresses the inflammatory response in septic cardiac dysfunction are unknown. To study this, rat H9c2 cardiomyocytes were treated with gastrodin and/or lipopolysaccharide (LPS). Our results showed that gastrodin treatment strongly suppressed nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) family activation and upregulation of the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in LPS-stimulated H9c2 cardiomyocytes. Simultaneously, gastrodin obviously upregulated the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling in a dose-dependent manner. However, wortmannin, a specific PI3-K inhibitor, blocked the inhibitory effects of gastrodin on LPS-stimulated H9c2 cardiomyocytes. Furthermore, PI3-K/Akt inhibition partially abolished the inhibitory effects of gastrodin on the phosphorylation of inhibitor kappa B-alpha (I kappa B-alpha), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and activity of NF-kappa B. Here we report activation of the PI3-K/Akt signaling by gastrodin and that inhibition of this pathway reverses the inhibitory effects of gastrodin on NF-kappa B and MAPKs activation in H9c2 cardiomyocytes. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：1124 / 1133

页数：10

共 37 条

[1]

DIFFERENTIAL SENSITIVITY TO LPS-INDUCED MYOCARDIAL DYSFUNCTION IN THE ISOLATED BROWN NORWAY AND DAHL S RAT HEARTS: ROLES OF MITOCHONDRIAL FUNCTION, NF-κB ACTIVATION, AND TNF-α PRODUCTION [J].