6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-κB signalling.
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-α, IL-1β, 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-κB, 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-κB 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.
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Yanli
Y
Li
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Bin
B
Xu
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Ming
M
Xu
Laboratory Animal Center, Dalian Medical University, Dalian 116044, China.
Dapeng
D
Chen
Central Laboratory, The First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
Yongjian
Y
Xiong
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Mengqiao
M
Lian
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Yuchao
Y
Sun
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Zeyao
Z
Tang
Department of Pharmacology, Dalian Medical University, Dalian 116044, China.
Li
L
Wang
Department of Physiology, Dalian Medical University, Dalian 116044, China.
Chunling
C
Jiang
Department of Pharmacology, Dalian Medical University, Dalian 116044, China. Electronic address: dmuppliny@dlmedu.edu.cn.
Yuan
Y
Lin
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use*; D018938:Caco-2 Cells; D002396:Catechols / Q000737:chemistry / Q000627:therapeutic use*; D005233:Fatty Alcohols / Q000737:chemistry / Q000627:therapeutic use*; D020939:Zingiber officinale / Q000737:chemistry; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002396:Catechols; D005233:Fatty Alcohols; D016328:NF-kappa B; C007845:gingerol; D048051:p38 Mitogen-Activated Protein Kinases
6-Gingerol; Barrier function; Inflammation; Intestinal ischemia/reperfusion; Oxidative stress