PMID- 25929435 OWN - NLM STAT- MEDLINE DCOM- 20160203 LR - 20181113 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 64 IP - 6 DP - 2015 Jun TI - Higenamine regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal ischemia-reperfusion injury in mice. PG - 395-403 LID - 10.1007/s00011-015-0817-x [doi] AB - 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. FAU - Liu, Chao AU - Liu C AD - 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. FAU - Zhu, Chenyu AU - Zhu C FAU - Wang, Guangsheng AU - Wang G FAU - Xu, Rui AU - Xu R FAU - Zhu, Yaoming AU - Zhu Y LA - eng PT - Journal Article DEP - 20150501 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Alkaloids) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Protoporphyrins) RN - 0 (RNA, Small Interfering) RN - 0 (Tetrahydroisoquinolines) RN - 15442-64-5 (zinc protoporphyrin) RN - EC 1.11.1.7 (Peroxidase) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - TBV5O16GAP (higenamine) SB - IM MH - Alkaloids/*pharmacology/therapeutic use MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use MH - Epithelial Cells/drug effects MH - HMGB1 Protein/*drug effects/*metabolism MH - Heme Oxygenase-1/antagonists & inhibitors/*drug effects/*metabolism MH - Intestinal Diseases/*drug therapy MH - Laparotomy MH - Male MH - Mesenteric Artery, Superior/drug effects MH - Mice MH - Mice, Inbred C57BL MH - NF-E2-Related Factor 2/*drug effects/*metabolism MH - Peroxidase/metabolism MH - Protoporphyrins/pharmacology MH - RNA, Small Interfering/genetics MH - Reperfusion Injury/*drug therapy MH - Tetrahydroisoquinolines/*pharmacology/therapeutic use MH - Transfection EDAT- 2015/05/02 06:00 MHDA- 2016/02/04 06:00 CRDT- 2015/05/02 06:00 PHST- 2014/08/03 00:00 [received] PHST- 2015/04/02 00:00 [accepted] PHST- 2015/03/12 00:00 [revised] PHST- 2015/05/02 06:00 [entrez] PHST- 2015/05/02 06:00 [pubmed] PHST- 2016/02/04 06:00 [medline] AID - 10.1007/s00011-015-0817-x [doi] PST - ppublish SO - Inflamm Res. 2015 Jun;64(6):395-403. doi: 10.1007/s00011-015-0817-x. Epub 2015 May 1.