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Localized leptin release may be an important mechanism of curcumin action after acute ischemic injuries

Deng, Zi-Hui MS*; Liao, Jie MS*; Zhang, Jin-Ying MS; Hao, Xiu-Hua; Liang, Chen MS; Wang, Lu-Huan; Xue, Hui; Zhang, Kai MS; Yan, Guang-Tao MS

Journal of Trauma and Acute Care Surgery: April 2013 - Volume 74 - Issue 4 - p 1044–1051
doi: 10.1097/TA.0b013e3182826eba
Original Articles

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.

CONCLUSION 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.

From the Research Laboratories of Biochemistry (Z-H.D., J-Y.Z., X-H.H., C.L., L-H.W., H.X., K.Z., G-T.Y.), and Medical Experiment and Test Center (J.L.), Basic Medical Institute, General Hospital of PLA, Beijing, China.

Submitted: October 8 21, 2012, Revised: November 22, 2012, Accepted: November 27, 2012.

Address for reprints: Guang-Tao Yan, MS, Research Laboratory of Biochemistry, Basic Medical Institute, General Hospital of PLA, 28 Fuxing Rd, Beijing 100853, China; email:

*Z.-H.D. and JL contributed equally to this study.

© 2013 Lippincott Williams & Wilkins, Inc.