Proinflammatory cytokines such as tumor necrosis factor alpha have been identified to mediate tight junction defects contributing to diarrhea in inflammatory bowel diseases (IBD). In traditional Eastern medicine, diarrhea has been treated for a long time by the plant alkaloid berberine. In our study, we analyzed whether berberine may have reverse effects on TNFa-induced paracellular barrier impairment.

Methods: 

Confluent monolayers of HT-29/B6 human colon cells and rat colon epithelia were analyzed regarding the effects of TNFa and berberine in Ussing chambers in vitro. Tight junction protein localization and regulation were analyzed by Western blot and confocal laser scanning microscopy.

Results: 

TNFa induced a marked decrease of transepithelial resistance in both, HT-29/B6 cells and rat colon. On molecular level, a TNFa-induced removal of claudin-1 from the tight junction and an increased claudin-2 expression was observed. Berberine prevented the TNFa effect, and inhibitor studies revealed that this effect was mediated via tyrosine kinase, pAkt, and NFkB pathways. Moreover, berberine alone inhibited phosphorylation of P42/P44 and phospho P38.

Conclusions: 

The plant alkaloid berberine prevents TNFa-mediated impairment of paracellular barrier properties. Moreover these results may suggest novel therapeutic approaches for the treatment of inflammatory diseases (Supported by DFG FOR 721).