Fig. 6.

Cardiac glycosides inhibit TNF-α/NF-κB signaling by blocking recruitment of TRADD to the TNFR. The binding of TNF-α to TNFR1 initiates the TNF signal transduction pathway. TNFR1 recruits TRADD to form a complex with TNFR1. A series of additional adapter molecules then assemble sequentially on this platform, including TRAF2, RIP, and Fas-associated death domain (FADD), where they initiate downstream events leading to NF-κ B activation, JNK activation, and inflammation or apoptosis. Cardiac glycosides inhibit the TNF-α signaling pathway by blocking recruitment of TRADD to the TNFR.