Inflammation Research

, Volume 64, Issue 6, pp 395–403 | Cite as

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

  • Chao Liu
  • Chenyu Zhu
  • Guangsheng Wang
  • Rui Xu
  • Yaoming ZhuEmail author
Original Research Paper



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.


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.


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


Higenamine Nrf-2 HO-1 Hmgb1 Intestinal IR injury 


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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Chao Liu
    • 1
  • Chenyu Zhu
    • 1
  • Guangsheng Wang
    • 1
  • Rui Xu
    • 1
  • Yaoming Zhu
    • 1
    Email author
  1. 1.Department of General Surgery, Yichang Central People’s Hospital, The First College of Clinical Medical ScienceChina Three Gorges UniversityYichangChina

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