Chlorogenic acid improves intestinal barrier function by downregulating CD14 to inhibit the NF-κB signaling pathway

• We studied the role of chlorogenic acid (CGA) in intestinal barrier function. • CGA downregulated CD14 to block the NF/κB signaling pathway. • CGA inhibited proinflammatory cytokine secretion via its effect on NF/κB signaling. • CGA was highly effective at preserving cell membrane integrity. Chlorogenic acid (CGA) is a polyphenol compound present in plant foods. CGA is a differentially excreted gut microbial metabolite in fecal samples of irritable bowel syndrome model mice and normal control mice. Here, we aimed to clarify the protective effect of CGA on intestinal barrier function. We used Caco-2 cells to create an intestinal epithelial cell barrier model, and evaluated tight-junctional permeability with fluorescein isothiocyanate–dextran. We treated Caco-2 cells with lipopolysaccharide and CGA, and measured tight-junction protein expression, TLR4/NF-κB pathway activation, and proinflammatory cytokine levels. CGA blocked the NF-κB pathway by downregulating CD14 and p65, and preventing phospho-p65 from entering cell nuclei. CGA showed anti-inflammatory effects by suppressing tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 production, and thereby restored intestinal epithelial tight-junction integrity. In conclusion, CGA was highly effective at preserving cell membrane integrity, and inhibited proinflammatory cytokine secretion by downregulating CD14 to block the NF-kB pathway.