(Photographs: Gitoxin, Digitalis and Drimia)
Cardiac glycosides are triterpenoid glycosides similar to saponins and are the compounds having a remarkable effect on heart muscles and their functioning. They have long served as the main medical treatment to congestive heart failure and cardiac arrhythmia (irregular heart beats). Extracts or latexes of plants containing these compounds were and are used as to poison arrows among many tribes of Africa, Asia and South America, when due to high concentrations they cause a violent contraction of the heart muscle and result in death due to cardiac arrest. The beneficial effects of these compounds were discovered by accident when William Withering , in 1775, noted that a patient thought to be incurable, recovered from dropsy after being administered an infusion of various plant parts including a common garden plant, the Foxglove (Digitalis purpurea- Scrophulariaceae), a plant rumored to kill a child who happen to drink the nectar from flowers. The careful follow up studies of Withering lead to discover that the glycosides of the leaves have a strong effect on cardiac muscles. They are found to change the rhythm of the heart beat in such a way that the systolic contraction is lengthened so that the ventricle is emptied more completely. Now it is found that this decrease in rate of contractions is by acting on the cellular sodium-potassium ATPase pump.
These glycosides are similar to saponins in forming emulsions in water and a definite effect on the heart mostly promoting heart beats. These compounds differ from saponins in having an unsaturated lactone ring at C17¬ of the nucleus, a cis juncture of the rings C & D, an additional hydroxyl group at C14 and the unique sugars they possess. Of the two types of cardiac glycosides, cardenolides are C23 compounds possess a 5-membered lactone ring (e.g. Sarmentocymarin) and bufadienolides (scilladienolides) are C24 compounds with a doubly saturated 6-membered lactone ring (e.g., Scilliroside). Both cardenolides and bufadienolides are mutually exclusive in plant kingdom. The cardiotonic activity increases with the increase in hydroxyl groups of these glycosides. Their genins also exhibit these similar properties. All the sugars in the oligosaccharide are unique in that they are never seen outside, linked at C3 position, possess methyl and / or methoxy groups (e.g., digitalose) and the number of sugar units present in a glycoside ranges from 1 to 4.
Hundreds of cardiac glycosides have been found in many plants of Scrophulariaceae, Apocynaceae, Asclepiadaceae, Rubiaceae, Liliaceae etc. Traditionally, these substances were extracted from plants such as Digitalis purpurea or foxglove (Digitalis), Strophanthus gratus (Ouabain) or amphibian skin (Bufo marinus-bufalin, marinobufagenin).
Cardiac glycosides have long served as the main medical treatment to congestive heart failure and cardiac arrhythmia, due to their effects of increasing the force of muscle contraction while reducing heart rate. Heart failure is characterized by an inability to pump enough blood to support the body, possibly due to a decrease in the volume of the blood or its contractile force. Treatments for the condition thus focus on lowering blood pressure, so that the heart does not have to exert as much force to pump the blood, or directly increasing the heart's contractile force, so that the heart can overcome the higher blood pressure. Cardiac glycosides, such as the commonly used digoxin and digitoxin, deal with the latter, due to their positive inotropic activity. On the other hand, cardiac arrhythmia are changes in heart rate, whether faster (tachycardia) or slower (bradycardia). Medicinal treatments for this condition work primarily to counteract tachycardia or arterial fibrillation by slowing down heart rate, as done by cardiac glycosides.
Though cardiac glycosides have been used for their medicinal function, they also are found to affect the cardiovascular, neurologic, and gastrointestinal systems and produce toxic after effects. In addition, excessive cardiac glycoside dosage results in cardiac contractions with greater force, as further calcium is released from the SR of cardiac muscle cells. Toxicity also results in changes to heart chronotropic activity, resulting in multiple kinds of dysrhythmia and potentially fatal ventricular trachycardia. These dysrhythmias are an effect of an influx of sodium and decrease of resting membrane potential threshold in cardiac muscle cells. When taken beyond a narrow dosage range specific to each cardiac glycoside, these compounds can rapidly become dangerous. In sum, they interfere with fundamental processes that regulate membrane potential. The most common negative effect is premature ventricular contraction.
Nowadays, cardiac glycosides have been replaced with synthetic drugs such as ACE inhibitors and beta blockers, and are no longer used as the primary medical treatment for such conditions. Depending on the severity of the condition, though, they are still be used in conjunction with other treatments.
Recently, cardiac glycosides are increasingly being used in antitumor applications. More optimistic, many studies have confirmed that cardiac glycosides have selective killing effect on malignant tumor cells, that is, they do not affect the proliferation of normal cells, and may become a class of antitumor drugs with targeting effects. Several cardiac glycosides such as peruvoside have shown promise in cancer treatment, especially for ovary cancer and leukemia. Functional variability of these glycosides has revealed that not all cardiac glycosides are alike. Apart from their specific affinity to sodium-potassium ATPase, their therapeutic dosage and behavior in poly morbidity conditions needs to be considered.
The plants containing Cardiac glycosides, available with us, are the following.
1. Digitalis purpurea Linn.- Scrophulariaceae.
Contain more than 40 cardiac glycosides of which the two primary glycosides, purpurea glycosides A & B form the chief constituents of fresh leaves. Digitoxin is a cardiotonic increasing the tone of cardiac muscle. Gitalin alone or with other glycosides are often used in treatment of congestive heart failure. All these glycosides improve the rhythm of heartbeats, making the contraction of the heart more powerful and help the heart to pump the blood at the time of cardiac failure.
2. Digitalis lanata Ehrh. , common in India, yields more than 70 glycosides of which Digoxin – a triglycoside and the primary glycosides, lanatosides A, B, C, D and E are major ones. It is observed that, in all the glycosides showing cardiac activity. Lanatosides and digoxin are valuable cardiotonics.
3. Convallaria majalis Linn. - Liliaceae
Of the 25 or more glycosides isolated from the drug, the important ones are convallatoxin, convalloside and convallatoxol. The drug is a cardiotonic but has lesser action than Digitalis. Convallatoxin is an effective diuretic. Flower glycosides are found to strengthen and regulate heart action and in dropsy, they assist urine secretion.
4.Strophanthus kombe Oliv. And S. hispidus DC. - Apocynaceae
The seeds of these tall shrubs, native to Africa, provide the drug Strophanthus. The dry seeds yield about 8-10% Strophanthin or K-Strophanthin, a mixture of more than 10 glycosides. Strophanthus is the cardiotonic drug preferred to Digitalis in Europe.
5. Asclepias curassavica Linn.- Asclepiadaceae)
The leaves contain 22 cardenolides of which calactin, calotropin, calotropagenin and asclepin are the major compounds. The plant, as powder, balm or enema, is used to destroy abdominal tumours. The latex is used against warts and corns.
6. Carissa carandas Linn. - Apocynaceae
The roots contain cardiac glycosides based on odoroside H.
All parts of the plant are attributed with medicinal properties. Roots are cardiotonic, anthelmintic and effect a prolonged blood pressure lowering effect.
7. Cerbera manghas Linn.- Apocynaceae
All parts of the plant contain cardiac glycosides. The bark and leaves are cathartic and emetic. Seeds are fish poisons. Seed oil is used as hair oil and as a rubefacient to cure cold.
8. Calotropis gigantea Ait.f. and C. procera Ait.f - Asclepiadaceae
The root bark, which constitutes the drug, yields cardiac glycosides such as gigantin, giganteol, isogiganteol, calotroposides A-G etc. In Indian systems of medicine the tender fresh leaves are used to cure fits and convulsions in children and for migraine.
9. Corchorus olitorius Linn.- Tiliaceae
Seeds contain cardenolides such as olitoriside A, erysimoside, coroloside, etc. Seeds are ecbolic in nature and are used as a cardiotonic. The cardenolides are very effective in acute and chronic cardiac insufficiency, peroxystic tachycardia and tachyarythmia.
10. Pergularia daemia Choiv.- Asclepiadaceae
Stem and seeds contain cardenolides such as calactin, calotropin, calotropagenin (from seeds) uzarigenin, coroglaucigenin (from stems). The plant is used for vesical calculus, dysurea and anurea.
11. Nerium oleander Linn.- Apocynaceae
The bark yields a number of cardiac glycosides designated as odoroside A,B,D,F,G,H,K-M, odorobioside K etc. The root, the official drug, is considered highly toxic, but in controlled doses it is a cardiotonic.
12. Leptadenia reticulata W. & A. - Asclepiadaceae
The plant contains pregnane glycosides reticulatin, deniculatin and leptaculatin. Roots are considered a rasayana (tonic) drug, useful for vitalizing the body.
13. Thevetia peruviana Merril. - Apocynaceae
All parts of the plant contain cardiac glycosides; Seeds being the richest source of these compounds (containing up to 7 times) than the other parts. All the glycosides are used as cardiotonics, the most preferred ones being peruvoside and thevetin.
14. Helleborus niger Linn.- Ranunulaceae)
Rhizomes and parts of the aerial stem contain hellebrin which is supposed to have approximately twenty times powerful action compared to Digitalis – and so is extensively used in veterinary practices.
15. Drimia indica Jessop - Liliaceae (Scilla/ Urginea)
Bulbs contain bufadienolides (maximum in dormant stage of the bulb) such as proscillaridin A, scillopheoside and anhydroscilliphaosidin. They are used as an expectorant, cardiac stimulant and diuretic. It is also useful as an anticancer and hypoglycaemic drug and for skin diseases. This is used as a substitute to Digitalis when the patients show hypersensitivity to the former drug.
References:
1. Useful Herbs of the Planet Earth, by M. Daniel, (2012), Scientific Publishers, Jodhpur, Pages 399- 402
2. Google searches.
Mammen Daniel
