Taxifolin ameliorates lipopolysaccharide-induced intestinal epithelial barrier dysfunction via attenuating NF-kappa B/MLCK pathway in a Caco-2 cell monolayer model

Senegalia macrostachya seed polysaccharides attenuate inflammation-induced intestinal epithelial barrier dysfunction in a Caco-2 and RAW264.7 macrophage co-culture model by inhibiting the NF-κB/MLCK pathway

“…A disruption of the TJ structure leads to a loss of the intestinal barrier function, which might result in the development of enteropathies. 46,50,54,61 In previous studies, the pro-inflammatory factor TNF-α downregulated occludin promoter activity and caused redistribution of occludin, ZO-1, and claudin-1 protein. 54,79,80 In the present study, a significant decrease in TJ ZO-1, occludin, and claudin-1 protein was found in the LPS group.…”

“…Similar results were found elsewhere. 46,63 Interestingly, SMSP2 treatment attenuated the production of pro-inflammatory mediators at the mRNA level. Similarly, Ganoderma atrum polysaccharides inhibited pro-inflammatory cytokines, reactive oxygen species (ROS), and COX-2 release in LPS-induced Caco-2 cells and the RAW264.7 macrophage co-culture inflammation model.…”

“…Several studies have used LPS alone or in combination with inflammatory cocktails consisting mainly of TNF-α, IFN-γ, and IL-1β to induce intestinal inflammation. Although such models successfully induced intestinal epithelial cell inflammation, 12,46,[48][49][50][51] they might not give an exact representation of the complex in vivo inflammation status, characterized by the production and interaction of multiple cytokines and chemokines but not solely a defined set of cytokines. 41 In addition, most of the concentrations of the cytokines used in those studies are sometimes above the in vivo physiological achievable level.…”

“…45 Studies have indicated that the NF-kB-MLCK pathways play a pivotal role in the pathophysiological regulation of intestinal barrier integrity. 46,47 Previous studies revealed that NF-kB activation mediates the subsequent activation of the MLCK pathway resulting in an increased expression of channel formation junctional proteins and decreased expression of tight junction proteins. 48,49 In the current study, the inflammatory challenge induced a significant increase in TLR4 and NF-kB protein expression in the LPS group, while SMSP2 treatment markedly lowered the expression of these proteins (Fig.…”

“…The inhibition of the NF-kB pathway is recognized as a potential strategy to reduce intestinal inflammation. 46,62,73 Previous studies have shown that plant-derived polysaccharides alleviate gut inflammation by modulating the intestinal immune status through inhibition of the NF-kB pathway. 3,74,75 In the current study, SMSP2 treatment reduced NF-kBp65 protein phosphorylation in the Caco-2 cells.…”