Hydroxyxanthone ameliorates IL1β-induced epithelial barrier disruption in colonic-like cells by down-regulation of p-MLC expression

Abstract

Hydroxyxanthones, the synthetic form of xanthones that predominantly found in mangosteen (Garcinia mangostana), have been indicated as a potent anti-inflammatory action. This study aimed to examine the action of various HDX forms in preventing a tight junction (TJ) barrier disruption induced by TNF-α or IL-1β through the inhibition of p-MLC expression in Caco-2 cell model. TJ barrier function was determined by transepithelial electrical resistance (TER) and flux measurement of fluorescein isothiocyanate-dextran (FD-4). 1-monoHDX or 1,3-diHDX (10 μM) promoted TER but not FD-4 permeability in the absence of cytokines. Pretreatment with 1-monoHDX at 10 μM for 24 h prevented TNF-α or IL-1β effect on TJ permeability. p-MLC protein expression by Western blot analysis, which was induced by IL-1β was inhibited with all HDXs. Tricyclic scaffold as the basic skeleton of all HDXs may be a potential candidate therapeutic for treatment of diseases-related leaky gut. © 2021