A cardenolide is a type of

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

. Many plants contain derivatives, collectively known as cardenolides, including many in the form of cardenolide

glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

s (cardenolides that contain structural groups derived from sugars). Cardenolide glycosides are often

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

; specifically, they are heart-arresting. Cardenolides are toxic to animals through inhibition of the enzyme Na⁺/K⁺-ATPase, which is responsible for maintaining the sodium and

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

ion gradients across the cell membranes.

Etymology

The term derives from ''card-'' "heart" (from

Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...

καρδία ''kardiā'') and the suffix , referring to the lactone ring with double bond at C17. Cardenolides are a class of steroids (or aglycones if viewed as

cardiac glycoside Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses include treatments for ...

constituents), and cardenolides are a subtype of this class (see MeSH D codes list).

Structure

Cardenolides are C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone (specifically a

butenolide Butenolides are a class of lactones with a four-carbon heterocycle, heterocyclic ring structure.Joule JA, Mills K. (2000). Heterocyclic Chemistry 4th ed. Blackwell Science Publishing: Oxford, UK They are sometimes considered redox, oxidized deri ...

) at C-17. They are aglycone constituents of cardiac glycosides and must have at least one double bond in the molecule. The class includes cardadienolides and cardatrienolides. Members include: * acetyldigitoxins * acetyldigoxins * cymarine *

digitoxin Digitoxin is a cardiac glycoside used for the treatment of heart failure and certain kinds of heart arrhythmia. It is a phytosteroid and is similar in structure and effects to digoxin, though the effects are longer-lasting. Unlike digoxin, whic ...

* digitoxigenin * digoxigenin *

digoxin Digoxin (better known as digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart disease, heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ...

* medigoxin * neoconvalloside * ouabain * strophanthidin

Bufadienolide Bufadienolide is a chemical compound with steroid structure. Its derivatives are collectively known as bufadienolides, including many in the form of bufadienolide glycosides (bufadienolides that contain structural groups derived from sugars). These ...

and marinobufagenin are similar in structure and function. Cardanolide is the same core structure, but has a saturated lactone ring instead of one containing an

alkene In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins. The Internationa ...

As defense mechanism

Some plant and animal species use cardenolides as defense mechanisms, notably the milkweed butterflies. Species such as the

monarch A monarch () is a head of stateWebster's II New College Dictionary. "Monarch". Houghton Mifflin. Boston. 2001. p. 707. Life tenure, for life or until abdication, and therefore the head of state of a monarchy. A monarch may exercise the highest ...

queen Queen most commonly refers to: * Queen regnant, a female monarch of a kingdom * Queen consort, the wife of a reigning king * Queen (band), a British rock band Queen or QUEEN may also refer to: Monarchy * Queen dowager, the widow of a king * Q ...

, and plain tiger ingest the cardenolides contained in the milkweeds (''Asclepias'') that they mostly feed on and sequester as larvae for defense as adults. The cardenolide content in butterflies deters most vertebrate predators, except a few which have evolved to become cardenolide-tolerant, such as the black-backed orioles (''Icterus abeillei'' Lesson) and black-headed grosbeaks (''Pheucticus melanocephalus'' Swainson) that account for 60% of monarch butterfly mortalities in the overwintering sites in central

Mexico Mexico, officially the United Mexican States, is a country in North America. It is the northernmost country in Latin America, and borders the United States to the north, and Guatemala and Belize to the southeast; while having maritime boundar ...

. In addition to milkweeds and other members of the

Apocynaceae Apocynaceae (, from '' Apocynum'', Greek for "dog-away") is a family of flowering plants that includes trees, shrubs, herbs, stem succulents, and vines, commonly known as the dogbane family, because some taxa were used as dog poison. Notable mem ...

, plants in at least 12 botanical families have convergently evolved cardenolides, used as a chemical defense mechanism against herbivores. Herbivorous insects in six different orders have evolved resistance to the toxic effects of cardenolides in the food sources that they use. These cardenolide-resistant insect species convergently evolved this resistance through similar amino-acid substitutions in the alpha subunit of the enzyme Na⁺/K⁺-ATPase.Dobler, S., Dalla, S., Wagschal, V., & Agrawal, A. A. (2012). Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase. Proceedings of the National Academy of Sciences, 109(32), 13040–13045. https://doi.org/10.1073/pnas.1202111109

References

* {{Cardiac glycosides