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

摘要

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 CD4sup+/supT 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) CD4sup+/sup T cells in T cell transfer IBD models in which SCID mice had been injected with CD4sup+/supCD45RBsuphigh/sup T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4sup+/sup 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 LPCD4sup+/sup T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4sup+/sup T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.