Berberine Ameliorates Intestinal Epithelial Tight-Junction Damage and Down-regulates Myosin Light Chain Kinase Pathways in a Mouse Model of Endotoxinemia

Abstract

BACKGROUND: This study aimed to examine the protective effect of berberine in endotoxin-induced intestinal tight-junction injury in a mice model of endotoxinemia. METHODS: Endotoxinemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Mice were randomized to 5 groups: control mice, berberine-treated mice, lipopolysaccharide (LPS)-injected mice, mice pretreated with berberine, and mice administered berberine following LPS injection. Samples were collected 12 h after LPS treatment. RESULTS: Ileal mucosal permeability to fluorescein isothiocyanate dextran assay indicated that berberine reduced the permeability of the gut barrier in endotoxinemia. Transmission electron microscopy revealed that pretreatement with berberine partly prevented ultrastructural disruption of tight junctions by LPS. Immunofluorescence and Western blot analysis were performed, and the results demonstrated that pretreatement with berberine partially reversed the redistribution of tight-junction proteins in colon epithelium and in membrane microdomains. Our data also indicated that pretreatement with berberine could suppress translocation, from cytoplasm to the nucleus, of nuclear factor-κB and myosin light chain kinase activation in the intestinal epithelium. CONCLUSIONS: Pretreatement with berberine attenuates disruption of tight junctions in intestinal epithelium in a mice model of endotoxinemia. This may possibly have been mediated through down-regulation of the nuclear factor-κB and myosin light chain kinase pathway.