Fig. 8

A schematic diagram that demonstrates the potential biological impact of A. millefolium extracts on C. difficile toxin-mediated inflammation. Exposure of intestinal epithelial cells (IECs) to A. millefolium extracts can lead to inhibition of NF-κB and TGF-β signaling pathways, which may decrease the expression of inflammatory cytokines like TNF-α, IL-8, and IL-1β. In addition, inhibition of iNOS activity by extracts can be one of the potential modulatory mechanisms affecting the suppression of apoptosis and inflammatory pathways mediated by C. difficile major toxins. On the other hand, A. millefolium extracts can inhibit inactivation of Rho/Ras proteins induced by toxins, resulting in apoptosis suppression. Moreover, they may inhibit apoptosis via downregulation of Bax and upregulation of Bcl-2, and then inactivate caspase cascades. Notes: red arrows indicate enhancing actions induced by toxins, whereas green arrows indicate inhibitory actions induced by A. millefolium extracts. Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; Cas-9: Caspase-9; Cas-3: Caspase-3; IECs: intestinal epithelial cells; IL-8: interleukin-8, IL-1β: interleukin-1β; iNOS: inducible nitric oxide synthase; NF-κB: nuclear factor kappa B; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor α