Cinnamomum cassia extract restores intestinal barrier function via the regulation of tight junction proteins under IL-6-induced inflammatory conditions

초록

Background Intestinal epithelial barrier dysfunction is a hallmark feature of inflammatory bowel disease and closely associated with tight junction (TJ) disruption and increased epithelial permeability. Cinnamon contains bioactive compounds with antioxidant and anti-inflammatory properties; however, its protective effects on intestinal barrier integrity remain unclear.Objective This study investigated whether Cinnamomum cassia ethanol extract (CNCE) protects against interleukin-6 (IL-6)-induced epithelial barrier dysfunction in Caco-2 cells by regulating TJ-associated proteins.Methods An IL-6-induced inflammatory barrier dysfunction model was established using Caco-2 cells. The antioxidant activity of CNCE was assessed using 2,2-diphenyl-1-picrylhydrazyl and 2,2 '-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays, and noncytotoxic concentrations were determined using cell viability analysis. Barrier function was evaluated using transepithelial electrical resistance (TEER) and 4-kDa fluorescein isothiocyanate (FITC)-dextran permeability assays. TJ protein localization and expression were examined by immunofluorescence staining and western blotting. LC-MS/MS and molecular docking analyses were performed to identify major CNCE-derived compounds and assess their potential interaction with zonula occludens-1 (ZO-1).Results CNCE exhibited concentration-dependent antioxidant activity and was noncytotoxic up to 100 mu g/mL. IL-6 reduced TEER and increased epithelial permeability, whereas CNCE pretreatment restored TEER values and reduced FITC-dextran permeability. Moreover, CNCE preserved the junctional localization of ZO-1 and occludin, restored their protein expression, and suppressed IL-6-induced claudin-2 upregulation. LC-MS/MS tentatively identified five major compounds in CNCE, including coniferaldehyde, coumarin, syringaldehyde, cinnamaldehyde, and 2-methoxycinnamaldehyde, and docking analysis suggested their potential interaction with ZO-1.Conclusion CNCE protects against IL-6-induced epithelial barrier dysfunction by preserving TJ structure and regulating TJ-associated protein expression, suggesting its potential as a natural barrier-protective agent for inflammatory intestinal disorders.

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