Berberine Ameliorates Ethanol-Induced Disruption of Intestinal Epithelial Tight Junction (GJGH V-1 I-1) - synergy - synergy

Berberine Ameliorates Ethanol-Induced Disruption of Intestinal Epithelial Tight Junction – Pages 58-65

Shanshan Sun1, Miao Wang1, Haiyan Song1, Weiwei Hao1 and Guang Ji1,2

1Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; 2E-Institute of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

DOI: http://dx.doi.org/10.12970/2308-6483.2013.01.01.9

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Abstract: Endotoxemia is a crucial factor contributes to alcoholic liver disease (ALD). The disruption of intestinal tight junction (TJ) caused by ethanol is one of the main underlying mechanisms. Berberine is used widely to treat gastrointestinal disorders and reportedly has beneficial effects on TJ integrity. The aims of the present study were to examine the effects of berberine on ethanol-induced intestinal epithelial TJ damage and explore the underlying mechanisms. Caco-2 cell monolayer was treated with ethanol to induce barrier damage. The effect of berberine on TJ was analyzed by measuring the transepithelial electrical resistance (TEER). Subcellular localization of TJ protein zonula occludens-1 (ZO-1) was determined by immunofluorescence microscopy. The expression levels of ZO-1, myosin light chain kinase (MLCK) and MLCK activation were analyzed by Real-time PCR and western blot. Intracellular calcium influx was measured by flow cytometry. The results showed that berberine treatment could significantly improve intestinal barrier function by decreasing intracellular calcium influx, inhibiting MLCK activation., and then reversing ZO-1 distribution. In conclusion, given that berberine also has antimicrobial and anti-inflammatory properties, the effects of berberine on endotoxins translocation are likely to be multifactorial, therefore, berberine should be a promising therapeutic option for ALD.

Keywords: Alcoholic liver disease, zonula occludens-1, intracellular calcium influx, myosin light chain kinase. Read more

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