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Toxic Monarchs and Heart Drugs

Toxic Monarchs and Heart Drugs

Monarch butterflies flaunt their gaudy colors because they are actively avoided by predators. Carissa Braun explains how these insects load themselves up with toxic milkweed compounds, the same toxins that have been used to treat failing heart for decades! 

Originally shared by Carissa Braun

Cardenolides and Monarchs

Monarchs require milkweeds in order to thrive, and many know it is because they rely on it and use that toxin as their own. The bright colors of the monarch are an indication to predators that they are unpalatable. Predators take heed allowing monarchs to leisurely fly to their next nectar destination undisturbed, but why?

Cardiac glycosides, known as cardenolides, are steroids characterized by a glycoside bond. There are at least 400 known cardenolides, and can be found in a number of plants including milkweed, foxglove, and oleander. Cardenolides inhibit the Na+,K+-ATPase (sodium pump) in vertebrates. Cardiac function is the key disruption, but the ionic balance of other animal cell types are as well including vascular smooth muscle, neurons, and kidney tubules. In the right dose, cardenolides can help treat heart failure and irregular heart beats. In the wrong dose, it can be fatal. 

One of the key features of cardenolides are the bitter taste. The cardenolides also are known to cause vomiting (emesis). As the emetic dose is approximately 50% of the lethal dose, fatal poisoning for herbivores is rare. Instead, most animals quickly associate vomiting with a plant containing cardenolides and avoid it.

Invertebrates are not spared by the Na+,K+-ATPase inhibition. Neuronal tissue is especially sensitive to cardenolides, particular the cardenolide ouabain. As it were, some species such as the Monarch butterfly have evolved a way not only around that issue, but to use it to their advantage as well. A modification in the sodium pump proteins confers resistance to the toxic cardenolides. For the Monarch, the ouabain binding site is of particular importance in determining their insensitivity to cardenolides.

The Na+,K+-ATPase is a protein. This protein consists of one alpha subunit of 1,016 amino acids and one beta subunit of 302 amino acids. Within the alpha subunit is the ouabain binding site. For Monarch butterflies, the change of a single amino acid within that binding site seems to contribute the most to insensitivity towards cardiac glyocsides. The switch of asparagine for histidine changes the receptor properties to a high degree and prevent ouabine from binding. From there, monarchs can sequester the toxin and incorporate it.

Foremost, cardenoalides are a plant defense mechanism. Monarchs evolved a way around that defense. The latex within the plants are yet another deterrent, and Monarchs yet again are finding a way pass by bleeding out the latex first before continuing to consume the milkweed. It is an evolutionary arms race where so far, it is monarchs (and their mimics) who are benefiting.

Additional Comments from Rajini Rao:

“Cardiac glycosides work by inhibiting the cardiac version of the sodium pump, sodium levels inside the heart cell. This drives another transport protein, sodium calcium exchanger in reverse, bringing more calcium into the heart cell. Calcium makes heart muscles contract, so the drug makes it easier for a failing heart to keep beating.”

#scienceeveryday  (but so close to #sciencesunday !)

Sources and Further Reading:

Saponins and Cardiac Glycosides (website)

Cardiac glycoside overdose (website)

Milkweeds, monarch butterflies and the ecological significance of cardenolides (pdf/website)

Molecular basis for the insensitivity of the Monarch (Danaus plexippus) to cardiac glycosides (pdf)

The Sodium-Potassium Pump (website)

Evolutionary Assembly of the Milkweed Fauna: Cytochrome Oxidase I and the Age of Tetraopes Beetles (pdf)


Join the Conversation


  1. Monarch caterpillars require milkweed that contains the cardenolides, Brian Freeman. Anything native to your area is best and Monarch Watch provides good guidelines:

    Of course, native can still be hard to come by. A debated alternative is Tropical Milkweed, Asclepias curassavica that is often easier to find. One to avoid, but is common to also find, is Butterfly Weed, Asclepias tuberosa, as it does not contain cardenolides. The adults may consume the nectar, but it will not help them propagate as the caterpillars will not eat it. A simple, rough test is to see if the milkweed produces the milky sap – usually a good indication of both latex and cardenolides.


  2. Brian Freeman, it depends on the species of milkweed. Some grow quite large, but can therefore take on more caterpillars whereas others are smaller and so you’d want more. I haven’t run into a problem with aggressive milkweed, so I don’t have much in the way of suggestions. If you do have excess, it might be worth getting in touch with a local native plant or butterfly society. They’re usually willing to grab it to give to others to help Monarchs, and depending on the volunteers, you may be lucky enough to have someone come remove them for you for replanting 🙂


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