Proposal of Therapeutic Strategy to Prevent the Relapse in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disorder of intestinal tract with intermittent episodes of remission and relapse. Although sustained clinical remission has recently been recognized as an important goal of IBD therapy, there are not many treatment options to maintain long-term remission. We have proposed that the enhancement of interleukin (IL)-10 production in the intestinal macrophages has the potential to be a novel therapeutic mechanism for maintaining the remission of IBD and found berberine as a candidate compound for IL-10 enhancer. In the present study, we developed a useful experimental animal model to evaluate the relapse phase of IBD and investigated the effect of berberine on this model. Berberine significantly attenuated colitis symptoms during the relapse phase of IBD relapse model. To further investigate how berberine enhances IL-10 production in intestinal macrophages, we explored target protein for berberine that controls this response. We detected fatty acid synthase (FAS) as a candidate target protein. FAS inhibitor suppressed the IL-10 production of macrophages enhanced by berberine in a concentration-dependent manner. This study suggests that FAS activators such as berberine may be useful in developing a novel therapeutic strategy aimed at preventing relapse in IBD.