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


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.


CONCLUSIONS
Our study provides evidence HG regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal IR injury in mice.
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
C
Liu
Chenyu
C
Zhu
Guangsheng
G
Wang
Rui
R
Xu
Yaoming
Y
Zhu
D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D004847:Epithelial Cells / Q000187:drug effects; D024243:HMGB1 Protein / Q000187:drug effects* / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D007410:Intestinal Diseases / Q000188:drug therapy*; D007813:Laparotomy; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000187:drug effects* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D014162:Transfection
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011524:Protoporphyrins; D034741:RNA, Small Interfering; D044005:Tetrahydroisoquinolines; C017803:zinc protoporphyrin; D009195:Peroxidase; D051547:Heme Oxygenase-1; C012348:higenamine