Berberine ameliorates TNBS induced colitis by inhibiting inflammatory responses and Th1/Th17 differentiation.

Abstract Th1 and Th17 cells, and their associated cytokines, have been associated with the pathogenesis of Crohn’s disease. Berberine (BBR), a compound long used in traditional Chinese medicines, has been reported to have therapeutic effects in treating experimental colitis. In this study, we show that BBR had a protective effect on mice with TNBS-induced colitis. BBR inhibited levels of IFN-γ, IL-17, IL-6, IL-1β and TNF-α both in the local colon and sera, and transiently increased levels of IL-22. BBR also markedly increased sIgA expression in the colon. BBR had pronounced effects on macrophage populations. Treatment with BBR adjusted the M2/M1 ratio. In addition, BBR exerted effects on adaptive immunity by suppressing numbers of Th1 and Th17 cells, as well as expression levels of their associated cytokines and transcriptional factors. BBR downregulated STAT3 and STAT1 phosphorylation, and inhibited phosphorylation of NF-kB. In vitro experiments showed that BBR inhibited the differentiation of Th17 and, to a lesser degree, Th1 cells, without affecting regulatory T cells. Therefore, we conclude that BBR plays a regulatory role in modulating the balance of immune responses in TNBS-induced colitis. Our study will help us understand the regulatory mechanisms exerted by BBR in the treatment of IBD.