Gallic acid serves as an effective therapeutic agent of inflammatory bowel disease: Pharmacological impacts on tight junction-dependent intestinal permeability in vivo and its related intracellular signaling.

Intestinal tight junction disruption contributes to the pathogenesis of inflammatory bowel diseases (IBD). We have recently reported that gallic acid was able to enhance intestinal tight junction assembly via CaMKK-β/AMPK/SIRT-1/ERK-dependent mechanisms with unknown possible therapeutic applications in IBD. The main aims of this study are to investigate the in vivo effects of gallic acid in experimental colitis mice and to search for feasible mechanisms of action. Here, we found that gallic acid attenuated weight loss, reduced disease activity index, and reversed colon length shortening in DSS-induced colitis mice. Importantly, gallic acid also significantly increased survival rates of DSS-induced colitis mice. Based on histopathological analyses, gallic acid diminished immune cell infiltration and neutrophil activity in colitis tissues. Of particular interest, gallic acid significantly reduced gene expressions of proinflammatory cytokines, including TNF, IFN-γ, IL-1β, IL-6, and IL-8. In addition, gallic acid suppressed MLCK gene transcription and protein expression in DSS-induced colitis mice. Furthermore, gallic acid also enhanced the expression of tight junction proteins, including ZO-1 and occludin. Consistently, gallic acid reduced tight junction-dependent leak pathway permeability and was shown to increase SIRT-1 activity, AMPK, and ERK phosphorylation in colon tissues of DSS-induced colitis mice. This study not only explores anti-colitogenic impacts of gallic acid, but also sheds some light on the mechanisms of its action. According to our findings, gallic acid may be useful as an anti-colitogenic nutraceutical.