Pterostilbene Ameliorates DSS-Induced Intestinal Epithelial Barrier Loss in Mice via Suppression of the NF-κB-Mediated MLCK-MLC Signaling Pathway

The integrity of the intestinal barrier is critical for homeostasis. In this study, we investigated the protective effect of pterostilbene (PTE) on the intestinal epithelium barrier. In vitro results of transepithelial electrical resistance (TEER) in Caco-2 cells indicated that PTE counteracted tumor necrosis factor α (TNFα)-induced barrier damage. In vivo PTE pretreatment markedly ameliorated intestinal barrier dysfunction induced by dextran sulfate sodium (DSS). Notably, intestinal epithelial tight junction (TJ) molecules were restored by PTE in mice exposed to DSS. The mechanism study revealed that PTE prevented myosin light-chain kinase (MLCK) from driving phosphorylation of MLC (p-MLC), which is crucial for maintaining intestinal TJ stability. Furthermore, PTE blunted translocation of NF-κB subunit p65 into the nucleus to downregulate MLCK expression and then to safeguard TJs and barrier integrity. These findings suggest that PTE protected the intestinal epithelial barrier through the NF-κB- MLCK/p-MLC signal pathway.