Oregonin inhibits inflammation and protects against barrier disruption in intestinal epithelial cells
| Autor: | Sung Hee Lee, Geom Seog Seo, Jin-Hua Chi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Survival Immunology Anti-Inflammatory Agents Inflammation AMP-Activated Protein Kinases Occludin Tight Junctions 03 medical and health sciences 0302 clinical medicine Intestinal mucosa tert-Butylhydroperoxide Diarylheptanoids medicine Immunology and Allergy Humans Intestinal Mucosa RNA Small Interfering Pharmacology Chemistry NF-kappa B AMPK Epithelial Cells Transfection NFKB1 Intercellular Adhesion Molecule-1 Cell biology 030104 developmental biology Caco-2 Cyclooxygenase 2 030220 oncology & carcinogenesis Cytokines Tumor necrosis factor alpha medicine.symptom Caco-2 Cells HT29 Cells Heme Oxygenase-1 |
| Zdroj: | International immunopharmacology. 59 |
| ISSN: | 1878-1705 |
| Popis: | Background and aims Oregonin, a major diarylheptanoid derivative isolated from Alnus japonica , exerts anti-inflammatory effects; however, little is known about the effect of oregonin in intestinal inflammation. The current study investigated the potential of oregonin for clinical applications in the treatment of inflammatory bowel disease (IBD) and elucidated its underlying molecular mechanisms. Methods The anti-inflammatory effect of oregonin in tumor necrosis factor-α (TNF-α)-stimulated human intestinal epithelial HT-29 cells was investigated. In addition, the protective effect of oregonin was determined against disruption of the intestinal barrier in tert -butyl hydroperoxide ( t -BH)-stimulated human intestinal epithelial Caco-2 cells. Results Oregonin suppressed the expression of cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), IL-8, and IL-1β, and inhibited activation of nuclear factor κB (NF-κB) in HT-29 cells stimulated with TNF-α. Oregonin increased heme oxygenase-1 (HO-1) expression through the ERK1/2 and JNK-dependent signaling pathway, which contributed to the oregonin-mediated suppression of COX-2 expression in the HT-29 cells stimulated with TNF-α. Moreover, oregonin induced AMP-activated protein kinase (AMPK) activation. Knockdown of AMPK abolished the induction of HO-1 protein by oregonin and suppression of oregonin-mediated ICAM-1 and COX-2 expression in the HT-29 cells stimulated with TNF-α. Oregonin prevented the t -BH-induced increase in monolayer permeability through inhibition of the reduction in expression of zonula occludens-1 and occludin in Caco-2 cells. Targeting HO-1 by siRNA transfection attenuated the oregonin-mediated prevention of loss of tight junction proteins and increase in permeability. Conclusion The findings of this study suggest that oregonin is a potential candidate for treatment of IBD by preventing mucosal inflammation and barrier disruption. |
| Databáze: | OpenAIRE |
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