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Higenamine regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal ischemia–reperfusion injury in mice

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Abstract

Introduction

Intestinal ischemia and reperfusion (IR) syndrome is a life-threatening dilemma caused by diverse events. Higenamine (HG), an active ingredient of Aconiti Lateralis Radix Praeparata, has been traditionally used as a heart stimulant and anti-inflammatory agent in oriental countries. But the function of HG on intestine IR injury has never been investigated.

Materials and methods

Mice underwent a 2 cm midline laparotomy, and the superior mesenteric artery (SMA) was obstructed by micro-vascular clamp to induce intestinal ischemia.

Results

In our current study, HG increases mouse intestinal epithelial (IEC-6) cell viability through induced heme oxygenase-1 (HO-1) production in vitro. In our in vivo murine intestinal IR injury model, the increased HO-1 protein level and activity, decreased intestinal injury score, Myeloperoxidase (MPO) activity, and inflammatory cytokine expression induced by HG were all abolished with additional treatment of HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX). Furthermore, HG reduced high mobility group box-1 (Hmgb1) expression in IR injury-performed intestine which was inhibited by additional administration of ZnPPIX. And HG treatment significantly decreased HO-1 expression in nuclear factor erythroid 2-related factor (Nrf-2) SiRNA-transfected cells but not in control SiRNA-transfected cells.

Conclusion

Our study provides evidence HG regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal IR injury in mice.

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Authors and Affiliations

  1. Department of General Surgery, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, No.183, Yiling Road, Yichang, 443003, Hubei, China

    Chao Liu, Chenyu Zhu, Guangsheng Wang, Rui Xu & Yaoming Zhu

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  1. Chao Liu
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Correspondence to Yaoming Zhu.

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Responsible Editor: Graham R. Wallace.

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Liu, C., Zhu, C., Wang, G. et al. Higenamine regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal ischemia–reperfusion injury in mice. Inflamm. Res. 64, 395–403 (2015). https://doi.org/10.1007/s00011-015-0817-x

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  • DOI: https://doi.org/10.1007/s00011-015-0817-x

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