6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-κB signalling

被引：118

作者：

Li, Yanli ^{[1
]}

Xu, Bin ^{[1
]}

Xu, Ming ^{[1
]}

Chen, Dapeng ^{[2
]}

Xiong, Yongjian ^{[3
]}

Lian, Mengqiao ^{[1
]}

Sun, Yuchao ^{[1
]}

Tang, Zeyao ^{[1
]}

Wang, Li ^{[1
]}

Jiang, Chunling ^{[4
]}

Lin, Yuan ^{[1
]}

机构：

[1] Dalian Med Univ, Dept Pharmacol, Dalian 116044, Peoples R China

[2] Dalian Med Univ, Lab Anim Ctr, Dalian 116044, Peoples R China

[3] Dalian Med Univ, Affiliated Hosp 1, Cent Lab, Dalian 116044, Peoples R China

[4] Dalian Med Univ, Dept Physiol, Dalian 116044, Peoples R China

来源：

PHARMACOLOGICAL RESEARCH | 2017年 / 119卷

基金：

中国国家自然科学基金;

关键词：

Intestinal ischemia/reperfusion; 6-Gingerol; Inflammation; Oxidative stress; Barrier function; ISCHEMIA-REPERFUSION INJURY; SYSTEMIC INFLAMMATION; OXIDATIVE STRESS; CACO-2; CELLS; RAT MODEL; KINASE; PERMEABILITY; DYSFUNCTION; PATHOGENESIS; APOPTOSIS;

D O I：

10.1016/j.phrs.2017.01.026

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Intestinal ischemia reperfusion (I/R) injury caused by severe trauma, intestinal obstruction, and operation is one of the tough challenges in clinic. 6-Gingerol (6G), a main active ingredient of ginger, is found to have anti-microbial, anti-inflammatory, anti-oxidative, and anti-cancer activities. The present study was designed to characterize the potential protective effects of 6G on rat intestinal I/R injury and reveal the correlated mechanisms. Rat intestinal I/R model was established with clamping the superior mesenteric artery (SMA) and 6G was intragastrically administered for three consecutive days before I/R injury. Caco-2 and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury in vitro. The results showed that 6G significantly alleviated intestinal injury in I/R injured rats by reducing the generation of oxidative stress and inhibiting p38 MAPK signaling pathway. 6G significantly reduced MDA level and increased the levels of SOD, GSH, and GSH-Px in I/R injured intestinal tissues. 6G significantly decreased the production of proinflammatory cytokines including TNF-alpha, IL-1 beta, and IL-6, and inhibited the expression of inflammatory mediators iNOS/NO in I/R injured intestinal tissues. The impaired intestinal barrier function was restored by using 6G in I/R injured rats and in both Caco-2 and IEC-6 cells characterized by inhibiting p38 MAPK phosphorylation, nuclear translocation of NF-kappa B, and expression of myosin light chain kinase (MLCK) protein. 6G also reduced the generation of reactive oxygen species (ROS) in both Caco-2 and IEC-6 cells. In vitro transfection of p38 MAPK siRNA mitigated the impact of 6G on NF-kappa B and MLCK expression, and the results further corroborated the protective effects of 6G on intestinal I/R injury by repressing p38 MAPK signaling. In conclusion, the present study suggests that 6G exerts protective effects against I/R-induced intestinal mucosa injury by inhibiting the formation of ROS and p38 MAPK activation, providing novel insights into the mechanisms of this therapeutic candidate for the treatment of intestinal injury. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：137 / 148

页数：12

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