Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation

Abstract

Abstract The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4 + T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro , using lamina propria (LP) CD4 + T cells in T cell transfer IBD models in which SCID mice had been injected with CD4 + CD45RB high T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4 + T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo . BBR-fed mice showed AMPK activation in the LPCD4 + T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4 + T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.