title: Localized leptin release may be an important mechanism of curcumin action after acute ischemic injuries.
abstract: BACKGROUND
  Previous studies have demonstrated that both curcumin and leptin are protective factors against acute injuries. Here, we investigated whether leptin and its signaling pathway mediate the protective effects of curcumin.
  
  
  METHODS
  A solid dispersion of curcumin-polyvinylpyrrolidone K30 was prepared and administered intraperitoneally. In vivo intestinal ischemia/reperfusion (I/R) injury in mice determined the effects of curcumin administration on inflammation, oxygen radical production, and leptin expression. In vitro studies using the venous epithelial cell line ECV-304 examined hypoxia/reoxygenation-induced leptin expression and release after curcumin administration. Furthermore, the effects on the leptin-regulated ERK1/2 and p38 MAPK signaling pathways were also explored.
  
  
  RESULTS
  Intestinal I/R induced marked bowel injuries. Curcumin treatment significantly improved animal survival and reduced the pathologic injuries in the intestines. Furthermore, the elevated intestinal water content and levels of malondialdehyde, interleukin 1β (IL-1β) and IL-6 were significantly decreased, but levels of superoxide dismutase increased. Interestingly, we found that the decreased leptin and its receptor Ob-Rb were restored by curcumin administration. In addition, in vitro studies showed that curcumin increased leptin expression and release after hypoxia/reoxygenation-induced cell injuries. Moreover, curcumin treatment restored decreased ERK1/2 phosphorylation (p-ERK1/2) and inhibited overactive p38 (p-p38) after injuries, and the effect was reversed by a leptin-specific antibody or Ob-R blocker.
  
  
  CONCLUSIONS
  These data suggest that leptin and Ob-Rb-dependent ERK and p38 MAPK signaling pathways may be involved in curcumin protection against intestinal I/R injury, and leptin may be a potential target of curcumin in intestinal I/R injury and other related acute diseases.
authors.affiliation: Research Laboratories of Biochemistry, Basic Medical Institute, General Hospital of PLA, Beijing, China.
authors.forename: Zi-Hui
authors.initials: ZH
authors.lastname: Deng
authors.forename: Jie
authors.initials: J
authors.lastname: Liao
authors.forename: Jin-Ying
authors.initials: JY
authors.lastname: Zhang
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Hao
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.forename: Lu-Huan
authors.initials: LH
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Guang-Tao
authors.initials: GT
authors.lastname: Yan
mesh_terms: D000208:Acute Disease; D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D020738:Leptin / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D020738:Leptin; D003474:Curcumin