A cardenolide is a type of

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

. 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 ion gradients across the cell membranes.

Etymology

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

Greek Greek may refer to: Greece 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 ...

καρδία ''kardiā'') and the suffix ''-enolide'', referring to the lactone ring 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 are as treatments for co ...

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 heterocyclic ring structure.Joule JA, Mills K. (2000). Heterocyclic Chemistry 4th ed. Blackwell Science Publishing: Oxford, UK They are sometimes considered oxidized derivatives of furan. The ...

) at C-17. They are aglycone constituents of

cardiac glycosides 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 are as treatments for co ...

and must have at least one double bond in the molecule. The class includes cardadienolides and cardatrienolides. Members include: *

acetyldigitoxin Acetyldigitoxin is a cardiac glycoside. It is an acetyl derivative of digitoxin, found in the leaves of ''Digitalis'' species. It is used to treat cardiac failure, particularly that associated with tachycardia Tachycardia, also called tachyarr ...

s * acetyldigoxins *

cymarine Cymarin (or cymarine) is a cardiac glycoside. Plants of the genus ''Apocynum'', including ''Apocynum cannabinum ''Apocynum cannabinum'' (dogbane, amy root, hemp dogbane, prairie dogbane, Indian hemp, rheumatism root, or wild cotton) is a pe ...

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, w ...

digitoxigenin Digitoxigenin, a cardenolide, is the aglycone of digitoxin. Digitoxigenin can be used to prepare actodigin. In Lednicer's book on steroids, it is made from deoxycholic acid Deoxycholic acid is a bile acid. Deoxycholic acid is one of the se ...

digoxigenin Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants '' Digitalis purpurea'', '' Digitalis orientalis'' and '' Digitalis lanata'' (foxgloves), where it is attached to sugars, to form the glycosides (e.g. Lana ...

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

medigoxin Metildigoxin (INN, or medigoxin BAN, or methyldigoxin) is a cardiac glycoside, a type of drug that can be used in the treatment of congestive heart failure and cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhyth ...

neoconvalloside Neoconvalloside is a 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 ...

* ouabain *

strophanthin Strophanthins are cardiac glycosides in plants of the genus ''Strophanthus''. The singular may refer to: * g-Strophanthin, also known as ouabain * k-Strophanthin It is commonly used in euthanasia (lethal injections) See also

* Cardenolide {{C ...

s *

strophanthidin k-Strophanthidin is a cardenolide found in species of the genus ''Strophanthus''. It is the aglycone of k-strophanthin, an analogue of ouabain. k-strophanthin is found in the ripe seeds of Strophanthus kombé and in the lily Convallaria. K-St ...

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 Cardanolide is a steroid with a molecular weight of 344.531. See also * 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 ...

is the same core structure, but has a

saturated Saturation, saturated, unsaturation or unsaturated may refer to: Chemistry * Saturation, a property of organic compounds referring to carbon-carbon bonds ** Saturated and unsaturated compounds **Degree of unsaturation ** Saturated fat or fatty ac ...

lactone ring instead of one containing an

alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...

As defense mechanism

Some plant and animal species use cardenolides as defense mechanisms, notably the

milkweed butterflies Danainae is a subfamily of the family Nymphalidae, the brush-footed butterflies. It includes the Daniadae, or milkweed butterflies, who lay their eggs on various milkweeds on which their larvae (caterpillars) feed, as well as the clearwing butte ...

. Species such as the

monarch A monarch is a head of stateWebster's II New College DictionarMonarch 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 authority ...

queen Queen or QUEEN may refer to: Monarchy * Queen regnant, a female monarch of a Kingdom ** List of queens regnant * Queen consort, the wife of a reigning king * Queen dowager, the widow of a king * Queen mother, a queen dowager who is the mother ...

, and

plain tiger ''Danaus chrysippus'', also known as the plain tiger, African queen, or African monarch, is a medium-sized butterfly widespread in Asia, Australia and Africa. It belongs to the Danainae subfamily of the brush-footed butterfly Family (biology), fa ...

ingest the cardenolides contained in the

milkweeds ''Asclepias'' is a genus of herbaceous, perennial, flowering plants known as milkweeds, named for their latex, a milky substance containing cardiac glycosides termed cardenolides, exuded where cells are damaged. Most species are toxic to humans ...

(''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 grosbeak The black-headed grosbeak (''Pheucticus melanocephalus'') is a medium-sized, seed-eating bird in the family Cardinalidae. It is sometimes considered conspecific with the rose-breasted grosbeak (''P. ludovicianus'') with which it hybridizes on ...

s (''Pheucticus melanocephalus'' Swainson) that account for 60% of monarch butterfly mortalities in the

overwintering Overwintering is the process by which some organisms pass through or wait out the winter season, or pass through that period of the year when "winter" conditions (cold or sub-zero temperatures, ice, snow, limited food supplies) make normal activi ...

sites in central

Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...

. 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 Members of the ...

, plants in at least 12 botanical families have

convergently evolved Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last com ...

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