Figure 8. Scheme of endiandrin A action on ENaC-dependent Na⁺ absorption.

p38, ERK and JNK are involved in the synergism of endiandrin A to impact colonic ENaC function. TNF-α-triggered JNK activation, which is described to negatively regulate the GR, is suppressed by endiandrin A. Furthermore, together with TNF-α, endiandrin A induces a prolonged p38 phosphorylation, which stabilizes GR mRNA and increases GR protein levels. Endiandrin A facilitates the dexamethasone-induced GR nuclear translocation resulting in an enhanced GRE-transactivation and an increase of β- and γ-ENaC as well as sgk-1 expression. Endiandrin A activates ERK, which impinges on the ENaC. Dotted lines indicate signaling pathways inhibiting the colonic ENaC function.