Abstract: Objective The aims of this study is to determine whether berberine（BBR） has a protective effect on lipopolysaccharide（LPS）-induced intercellular high permeability in Caco-2 cells in vitro. Methods Caco-2 cells was incubated and divided into four groups,e.g. control（cultured in Dulbecco's modified eagle medium）,LPS（co-incubated with medium and 2 μg/ml of LPS,BBR （co-incubated with medium and 10μM BBR） and BBR/LPS group （co-incubated with medium,2μg/ml of LPS and 10μM BBR）. The morphological features of cell growth were observed under inverted microscope. Paracellular permeability was assessed by measuring transepithelial fluorescein permeability. Tight junction protein occludin and Toll-like receptors-4（TLR4） were detected by Western blotting. The expression of downstream signal molecule,MyD88,was detected by immunofluorescence. Results We observed that the intercellular junction were long and thin in control and BBR group, while a saw tooth fracture in intercellular junctions was found in LPS group and a coarse margin but without interruption was observed in BBR/LPS group;there were no significantly differences between control and BBR group as respect to fluorescein permeability （683.3±; 98.9 μg/ml vs. 849.0±; 89.7 μg/ml,respectively）,and the expression of occludin,TLR4 and MyD88 （P>; 0.05）;the fluorescein penetrating concentration （1886±; 176.0 μg/ml） was much higher,TLR4 expression increased,occludin expression decreased,and enhanced MyD88 fluorescence signal in cytoplasm was observed in LPS group as compared with in control group（P<; 0.05）;the fluorescein penetrating concentration（1071.0±; 65.9 μg/ml） and TLR4 expression decreased,occludin expression increased, and weakened MyD88 fluorescence signal in cytoplasm was observed in BBR/LPS group as compared with LPS group （P<; 0.05）. Conclusion Our findings suggest that BBR alleviates LPS-induced intercellular high permeability by weakening TLR4/MyD88 activity and increasing the expression of occludin.

Key words: Caco-2 cells, Berberine, Lipopolysaccharide, Occludin, Tight junction