FIGURE 3.

The direct and indirect inhibitory effects of berberine on autoreactive Th17 and Th1 cells. Through the direct route, berberine suppresses differentiation of CD4 cells into Th17 and Th1 cells and inhibits activation of these cells through decreasing expression of TNF and IL17 cytokines via inhibiting STAT3 and RORgt. Through the indirect route, berberine suppresses the activation of both Th17 and Th1 cells via modulating the activity of macrophages and DCs via suppressing the production of inflammatory cytokine. Further suppressive effect of berberine on Th17 and Th1 cells is achieved through its promoting impact on Treg differentiation and activation via inducing activity of AhR transcription factor, CYP1A1 and Foxp3. Green and red arrows reflect promoting and inhibiting effects of berberine, respectively