Glycosides are organic or synthetic substances that result from the reversible condensation of two or more ring-shaped sugars or from the condensation of a sugar with a wide variety of alcohols via a so-called glycosidic bond, in each case splitting off an H2O molecule. Glycosides are synthesized by many plants in an almost incalculable variety, and some of them have a high medical importance for humans, for example as cardiac glycosides or as so-called aminoglycoside antibiotics.
What are glycosides?
Some of the glycosides, such as certain flavonoids and so-called cardiac glycosides, are important as medicinal agents in the manufacture of medicines. Glycosides or glycosides are organic compounds in which at least one alcohol residue (R-OH) is linked to the anomeric C atom of at least one sugar residue via a glycosidic bond. The glycosidic bond is formed by condensation of a cyclic sugar with an alcohol residue or another sugar. The sugar may have a five-membered ring or a six-membered ring, each with a different designation. In each glycosidic bond, one molecule of water (H2O) is split off. The glycosidic bond is so widespread and so diverse in plants that it can be compared in importance to the peptide bond in the construction of polypeptides and proteins. There exists an almost unmanageable variety of glycosides, which is further enhanced due to the different three-dimensional structure of the molecules with the same chemical molecular formula. Glycosides can not only be synthesized via metabolic processes in plant cells, but a few are also produced industrially using enzymatic or non-enzymatic processes. Some of the glycosides, such as certain flavonoids and so-called cardiac glycosides, have importance as medicinal agents in drug production.
Pharmacological action
Some glycosides are used by plants to defend themselves against pathogenic germs or to protect themselves from predators. Needed toxins can be stored in the form of a glycoside as an inactive toxin in small cell inclusions (vacuoles or lysosomes). When needed, the inactivated toxin can be released and reactivated by a specific glycosidase that matches the glycoside. Some glycosides are used by the pharmaceutical industry because of their pharmacological effects. These are mainly some flavonoids, cardiac glycosides and phenolic glycosides. Of the approximately 6,500 known flavonoids, a few show vascular enhancing effects. They can dampen inflammation by inhibiting histamine. Antispasmodic properties and antiviral effects of certain flavonoids are also known. Likewise, the antioxidant effects of flavonoids are appreciated. It should be noted, however, that the antioxidant effect of quercetin, which is found in many plants as a secondary ingredient, is cancelled out by consuming only a small amount of milk. Some flavonoids can lower total cholesterol levels without affecting HDL fractions, so that the important quotient of LDL cholesterol and HDL cholesterol actually improves. The target value of the quotient is three or less. Through their antioxidant properties, some naturally occurring flavonoids (apples, green tea, blueberries, cranberries, onions) are also believed to have a certain protective effect against cancer. Of particular importance are the so-called cardiac glycosides, which, in the case of digitalis glycosides, can increase the contractile force of the heart muscle, reduce heart rate, and slow electrical conduction. Cardiac glycosides are found not only in the familiar foxglove (digitalis), but also in many other plants such as Adonis rose, bishop’s weed, lily of the valley, and several others. The skin of some poisonous toads contains cardiac glycosides in the form of bufadienolides, which were used as arrow poisons. From the group of phenolic glycosides or phenylglycosides, arbutin and various anthraquinones have special pharmacological importance because of their laxative action.
Medicinal use and application
In addition to the antioxidant effects of certain flavonoids, a long-term study from California demonstrated that fisetin, a flavonoid found in wig shrub, has beneficial effects on long-term memory.Digitalis glycosides, which are obtained from the woolly foxglove and the red foxglove, among others, are used for their pharmacological effects in cardiac insufficiencies and in sinus or AV node-induced tachycardia (heart palpitations) with a beat rate permanently above 100 beats per minute. Cardiac glycosides such as digoxin and digitoxin are often given in combination with an ACE inhibitor and/or a beta blocker, as well as a diuretic. Arbutin and some antraquinones, both substances belonging to the phenolic glycosides, are used pharmacologically because of their laxative effect. Both active substances are frequently components of laxatives. It should be noted that hydroquinone, a remodeling product of arbutin, should not be taken more than five times a year for no longer than a week at a time, as it can damage the liver in higher doses.
Risks and side effects
In drug therapy containing the cardiac glycosides digoxin and digitoxin, it must be remembered that the half-life of digoxin is 1.5 days and that of digitoxin, because of the enterohepatic circulation, is as long as 7 days. This means that gastric lavage and administration of activated charcoal are necessary in case of overdose, which can lead to serious cardiac arrhythmias as well as visual disturbances and malaise and vomiting. In addition, the enterohepatic circulation can be interrupted with colestyramine, resulting in increased excretion of digitoxin. Cyanogenic glycosides are frequently found in plants in their green leaves. They serve as protection against predators. The damaged leaves release both the cyanogenic glycoside and the corresponding glycosidase, which breaks down the glycoside and leads to the release of the hydrocyanic acid (cyanide). Cyanide (HCN) is highly toxic to almost all organisms, as it paralyzes the respiratory chain and leads to symptoms of poisoning within seconds. However, the concentration of cyanogenic glycosides in the leaves of plants is usually so low that there is no danger to humans. Widely known is the cyanogenic glycoside amygdalin, which is present in the kernels of bitter almonds and apricots and can cause symptoms if consumed in excess.
