Oxyresveratrol improves tight junction integrity through the PKC and MAPK signaling pathways in Caco-2 cells.

Strengthening intestinal tight junctions (TJ) provides an effective barrier from the external environment and is important for recovery from inflammatory bowel disease. Oxyresveratrol (OXY), an isomer of hydroxylated resveratrol, is isolated from many plants. The aim of this study was to investigate the effect of OXY on intestinal TJ and to elucidate the mechanism underlying the OXY-mediated increase in TJ integrity in human intestinal Caco-2 cells. OXY-treated Caco-2 cell monolayers showed decreased monolayer permeability as evaluated by paracellular transport assay. The results showed that OXY significantly increased the levels of TJ-related genes and proteins (Claudin-1, Occludin and ZO-1) compared with those of the negative control. OXY activated protein kinase C (PKC) and increased expression levels of mitogen-activated protein kinase (MAPK) genes. OXY also increased gene and protein levels of the transcription factor Cdx-2. Expression levels of TJ, PKC and Cdx-2 proteins and transepithelial electrical resistance (TEER) value decreased in OXY-treated Caco-2 cells following treatment with a pan-PKC inhibitor compared with those of the untreated control. In conclusion, OXY strengthens the integrity of the intestinal TJ barrier via activation of the PKC and MAPK pathways.