Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells.

Abstract

The potential of natural phytochemicals in addressing ethanol-related public safety concerns has been garnering attention. Galangin, a potent flavonoid renowned for its antioxidative and anti-inflammatory characteristics, is derived from the galanga plant, and propolis is derived from bees. Here, we documented the effects of galangin on ethanol-stimulated intestinal tight junction damage and investigated its potential protective mechanism in both in vivo and in vitro models, which has not been extensively investigated. Our results revealed that galangin efficaciously mitigated ethanol-induced intestine injury and dysfunction of the intestinal barrier. Concurrently, galangin significantly counteracted the ethanol-induced upregulation of NLRP3 inflammasome-associated proteins and activated the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in both the mouse colon and Caco-2 cells. Interestingly, similar to galangin, inhibitors of MAPKs and the NF-κB p65 reduced ethanol-induced NLRP3 inflammasome activation and intestinal tight junction damage. To sum up, our results showed that galangin blocks the ethanol-induced perturbation of the intestinal barrier and activation of the NLRP3 inflammasome via the NF-κB/MAPK signaling pathways.