Arenobufagin is a cardiotoxic bufanolide steroid secreted by the Argentine toad Bufo arenarum.

Arenobufagin is specifically secreted by Rhinella arenarum, which is found in South America.

Toads produce their venom when they are scared, injured, or provoked, as a defense mechanism against their predators.

In fact, this compound showed the most potent antitumor activity of fifteen bufadionolides isolated from Chan’su.

Toad venom is in fact still used in clinical practice of in TCM to treat hepatocellular carcinoma (HCC).

One studie shows that Arenobufagin inhibits VEGF-induced endothial cell tube formation.

Arenobufagin is believed to play a role in the regulation of the transport of water and electrolytes across cell membranes under physiological conditions.

It has been suggested that uncharged and non-polar amino acids may participate in the binding of arenobufagin to the extracellular surface of the ATPase.

Last but not least, specific cleavage of poly (ADP-ribose) polymerase (PARP) and a decrease in pro-caspase9 and 3 were also induced by arenobufagin treatment.

Arenobufagin also leads to increased expression of LC3-II, Biclin1(initial vesicle formation), Atg5 (elongation and completion), Atg9, Atg16L1 and p62/SQSTM1, all proteins which induce autophagy.

It was hypothesized that arenobufagin may inhibit the PI3K/Akt pathway in controlling cell death and differentiation in response to external stimuli.

The biotransformation processes consists of a main reaction whereas the dehydrogenation of the 3-hydroxyl group takes place.

Cardiac glycosides are natural compounds found in plants which cause inactivation of the sodium potassium pump like arenobufagin.