Curcumin Ameliorates Hydrogen Peroxide-Induced Epithelial Barrier Disruption by Upregulating Heme Oxygenase-1 Expression in Human Intestinal Epithelial Cells
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Disruption of epithelial tight junctions (TJ) followed by loss of barrier function is of crucial importance in the pathogenesis of a variety of gastrointestinal disorders. Heme oxygenase-1 (HO-1), which can be induced by curcumin (Cur), provides protection against various forms of oxidative stress.
The protective effect of Cur on oxidative stress-induced intestinal barrier disruption in human intestinal epithelial cells was elucidated in this study.
H2O2-induced Caco-2 enterocytic monolayers were incubated in the presence or absence of Cur and/or zinc protoporphyrin (ZnPP). The trans-epithelial electrical resistance (TEER) and the flux of sodium fluorescein in the filter-grown Caco-2 cell monolayers were measured. The expression and localization of the TJ protein occludin and zonula occluden-1 (ZO-1) were evaluated by western blot and immunofluorescence microscopy. The mRNA and protein levels of HO-1 were analyzed by real-time PCR and western blot.
Cur attenuated H2O2-induced disruption of paracellular permeability (TEER 52.02 ± 10.15% vs 22.71 ± 3.11%; sodium fluorescein flux 12.41 ± 2.19% vs 32.00 ± 4.97%, P < 0.05) and induced HO-1 mRNA (6.64 ± 0.48 vs 3.22 ± 0.28, P < 0.05) and protein (291.00 ± 9.17% vs 99.00 ± 10.00%, P < 0.05) expression in Caco-2 cells. After administration of H2O2, occludin and ZO-1 proteins were restored by Cur (occludin 175.67 ± 29.50% vs 53.67 ± 24.19%, P < 0.05; ZO-1 139.67 ± 33.71% vs 36.00 ± 15.88%, P < 0.05) and this effect was blocked by HO-1 inhibitor, ZnPP (occludin 54.67 ± 10.02% vs 168.33 ± 36.47%, P < 0.05; ZO-1 50.00 ± 15.13% vs 117.67 ± 38.81%, P < 0.05).
Cur protects human intestinal epithelial cells against H2O2-induced disruption of TJ and barrier dysfunction via the HO-1 pathway.
KeywordsCurcumin Intestinal mucosal barrier Tight junction Heme oxygenase-1 Oxidative stress
Inflammatory bowel disease
Junctional adhesion molecule
Dulbecco’s Vogt modified Eagle’s media
Trans-epithelial electrical resistance
This work was supported in part by a grant to Huiqing Jiang from the National Natural Science Foundation of China (no. 81170411), the Natural Science Foundation of Hebei Province, China (no. C2010000530), and the Health Department Foundation of Hebei Province, China (no. 20090377).
Conflict of interest
- 20.Srinivasan A, Menon VP, Periaswamy V, Rajasekaran KN. Protection of pancreatich beta-cell by the potential antioxidant bis-o-hydroxycinnamoyl methane, analogue of natural curcuminoid in experimental diabetes. J Pharm Pharm Sci. 2003;6:327–333.Google Scholar