Cardenolide Glycosides (Asclepin)

Cardenolides bind to and inhibit the alpha subunit of the plasma membrane Na+/K+-ATPase enzyme, reducing sodium extrusion from cells and elevating intracellular calcium via Na+/Ca2+ exchange — the classic mechanism of positive cardiac inotropy shared with digitalis. At sub-cardiotonic doses present in A. tuberosa root extracts, cardenolides modulate signaling pathways associated with inflammation: Na+/K+-ATPase acts as a signal transducer activating Src kinase, which in turn phosphorylates EGFR and downstream MAPK/ERK and PI3K/Akt pathways involved in inflammatory gene expression. Additionally, some Asclepias cardenolides inhibit NF-κB nuclear translocation and suppress IL-1β-stimulated arachidonic acid release, providing a mechanistic basis for the traditional anti-pleuritic application.