Curcumin protects intestinal mucosal barrier function of rat enteritis via activation of MKP-1 and attenuation of p38 and NF-κB activation.
BACKGROUND
Intestinal mucosa barrier (IMB) dysfunction results in many notorious diseases for which there are currently few effective treatments. We studied curcumin's protective effect on IMB and examined its mechanism by using methotrexate (MTX) induced rat enteritis model and lipopolysaccharide (LPS) treated cell death model.


RESULTS
Curcumin was intragastrically administrated from the first day, models were made for 7 days. Cells were treated with curcumin for 30 min before exposure to LPS. Rat intestinal mucosa was collected for evaluation of pathological changes. We detected the activities of D-lactate and diamine oxidase (DAO) according to previous research and measured the levels of myeloperoxidase (MPO) and superoxide dismutase (SOD) by colorimetric method. Intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were determined by RT-PCR and IL-10 production was determined by ELISA. We found Curcumin decreased the levels of D-lactate, DAO, MPO, ICAM-1, IL-1β and TNF-α, but increased the levels of IL-10 and SOD in rat models. We further confirmed mitogen-activated protein kinase phosphatase-1 (MKP-1) was activated but phospho-p38 was inhibited by curcumin by western blot assay. Finally, NF-κB translocation was monitored by immunofluorescent staining. We showed that curcumin repressed I-κB and interfered with the translocation of NF-κB into nucleus.


CONCLUSIONS
The effect of curcumin is mediated by the MKP-1-dependent inactivation of p38 and inhibition of NF-κB-mediated transcription. Curcumin, with anti-inflammatory and anti-oxidant activities may be used as an effective reagent for protecting intestinal mucosa barrier and other related intestinal diseases.
Song
Wei-Bing
WB
Department of Gerontology, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China. songweibing@yahoo.com
Wang
Yuan-Yuan
YY
Meng
Fan-Su
FS
Zhang
Qing-Hua
QH
Zeng
Jian-Ying
JY
Xiao
Li-Ping
LP
Yu
Xin-Pei
XP
Peng
Dan-dan
DD
Su
Lei
L
Xiao
Bing
B
Zhang
Zhen-Shu
ZS
D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D004751:Enteritis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D003474:Curcumin