Cerberin

Cerberin is a type of cardiac glycoside, a steroidal class found in the seeds of the dicotyledonous angiosperm genus Cerbera; including the suicide tree (Cerbera odollam) and the sea mango (Cerbera manghas). This class includes digitalis-like agents, channel-blockers that as a group have found historic uses as cardiac treatments, but which at higher doses are extremely toxic; in the case of cerberin, consumption of the C. odollam results in poisoning with presenting nausea, vomiting, and abdominal pain, often leading to death. The natural product has been structurally characterized, its toxicity is clear—it is often used as an intentional human poison in third-world countries, and accidental poisonings with fatalities have resulted from individuals even indirectly consuming the agent—but its potentially therapeutic pharmacologic properties are very poorly described. Cerberin is a type of cardiac glycoside, a steroidal class found in the seeds of the dicotyledonous angiosperm genus Cerbera; including the suicide tree (Cerbera odollam) and the sea mango (Cerbera manghas). This class includes digitalis-like agents, channel-blockers that as a group have found historic uses as cardiac treatments, but which at higher doses are extremely toxic; in the case of cerberin, consumption of the C. odollam results in poisoning with presenting nausea, vomiting, and abdominal pain, often leading to death. The natural product has been structurally characterized, its toxicity is clear—it is often used as an intentional human poison in third-world countries, and accidental poisonings with fatalities have resulted from individuals even indirectly consuming the agent—but its potentially therapeutic pharmacologic properties are very poorly described. Cerberin, like all cardiac glycosides, has as its core a steroid-type set of four carbocycles (all-carbon rings). In cerberin, this steroid core is connected, first, to a separate oxygen-containing lactone ring (shown here, upper right of box), and second, to a sugar substituent (shown in infobox structure, left of image). There are two types of cardiac glycosides depending on the characteristics of the lactone moiety. Cerberin, with its five-membered ring, belongs to the cardenolide class; cardenolides are 23-carbon steroids with methyl groups at positions 10 and 13 of the steroid ring system, and the appended five-membered butenolide-type of lactone at C-17. Many types of sugars can be attached to cardiac glycosides; in the case of cerberin, it is an O-acetylated derivative of α-L-thevetose, which is itself a derivative of L-glucose (6-deoxy-3-O-methyl-α-L-glucopyranose). The cardenolide substructure to which the sugar is attached has also been independently characterised, and can be referred to as digitoxigenin (see image), hence, cerberin is, synonymously, (L-2'-O-acetylthevetosyl)digitoxigenin. As well, the non-acetylated structure was independently discovered and named neriifolin, and so cerberin is, synonymously, 2'-acetylneriifolin. Cerberin is soluble in chloroform, acetone, and, moderately, in water. The literature on cerberin toxicity, per se, remains sparse; unless otherwise specifically indicated, the following is general information regarding cardiac glycoside toxicity, with an emphasis on information from cardenolides (i.e., steroid natural products bearing the same digitoxigenin substructure). In poisoning situations, those who are poisoned by ingesting cardiac glycosides experience, within an hour, a variety of gastrointestinal and cardiac symptoms. For cerberin, these have been noted to include nausea, vomiting, and abdominal pain. Forensic sources indicate presentations for cardiac toxin poisonings that additionally include burning sensations in the mouth, diarrhea, headache, dilated pupils, irregular beating of the heart, and drowsiness; coma and death most often eventually follow. There is no clear, reported correlation between the dose and mortality (see below); death often occurs after 3–6 hours. A historic, reported lethal dose of cerberin in dog is 1.8 mg/kg, and in cat 3.1 mg/kg; that is, it is very low. Hence, eating the core of a fruit from the tree is sufficient for a human to receive a lethal dose, and consumption of the raw leaves of related oleander species has resulted in death. There is significant evidence both from Cerbera and from related species, with regard to lethal poisonings. Individual cases of poisoning from Cerbera, Nerium (oleander), and related species are documented including direct and indirect, and intentional and unintentional ingestion. In one case of accidental poisoning, two vegans in Europe that were foraging for and ingesting wild plants died after consuming wild oleander. In indirect cases, human consumption of crab, where the crustacean had earlier consumed plants producing cerberin or related cardenolides, fatalities are also known.