Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway.

Guo Zu,Ningwei Che,Jing Guo,Xiangwen Zhang,Tingting Zhou

doi:10.1038/srep38480

Abstract

Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

Highlights

Intestinal ischemia/reperfusion (I/R) injury occurs in multiple clinical settings, in liver and intestine transplantation, shock and mesenteric ischemic disease[1]
We propose that the protective effects of Rg1 on intestinal I/R injury involve the pro-inflammatory response, reactive oxygen species (ROS) generation and apoptosis in vivo
Intestinal damage was observed in a rat model undergoing 1 h ischemia followed by 6 h reperfusion

Summary

Introduction

Intestinal ischemia/reperfusion (I/R) injury occurs in multiple clinical settings, in liver and intestine transplantation, shock and mesenteric ischemic disease[1]. Recent studies showed that the Wnt/β-catenin signaling pathway, which regulates multiple biological and pathological processes, including ROS, apoptosis and inflammation, is likely involved in I/R injury pathogenesis. Activation of the Wnt/β-catenin pathway protects kidneys against I/R injury by attenuating apoptosis and inflammation of tubule epithelial cells[11]. An agonist of the Wnt signaling pathway attenuated liver injury and improved the survival of rats by decreasing ROS and apoptosis induced by hepatic I/R12. Recent studies revealed that Rg1 activates the Wnt/β-catenin signaling pathway in neural and endothelial cells[13,14]. Pretreatment with Rg1 reduced apoptosis and inhibited ROS production, which occurred in part by activating the Wnt/β-catenin signaling pathway in vivo and in vitro. The purpose of this study was to determine the effect of Rg1 on intestinal I/R injury models and explore the potential mechanisms underlying the protective effect of Rg1

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Conclusion