Silibinin
Encyclopedia
Silibinin also known as silybin, is the major active constituent of silymarin, standardized extract of the milk thistle seeds, containing mixture of flavonolignan
s consisting of among others of silibinin
, isosilibinin, silicristin and silidianin. Silibinin itself is mixture of two diastereomer
s Silibinin A and Silybinin B in approximately equimolar ratio. Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins. Silibinin has also demonstrated anti-cancer effects against human prostate adenocarcinoma cells, estrogen-dependent and -independent human breast carcinoma cells, human ectocervical carcinoma cells, human colon cancer cells, and both small and nonsmall human lung carcinoma cells.
Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (trade name Legalon SIL) a solution for injection
, is used in treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning. There is also clinical evidence for the use of silibinin as a supportive element in alcoholic and grade Child ‘A’ liver cirrhosis.
of silymarin led to the development of enhanced formulations. Silipide (trade name Siliphos), a complex of silymarin and phosphatidylcholine
(lecithin), is about ten times more bioavailable than silymarin. It has been also reported that silymarin inclusion complex with β-cyclodextrin
is much more soluble than silymarin itself. There have also been prepared glycoside
s of silybin, which show better water solubility and even stronger hepatoprotective effect.
Silymarin, as other flavonoid
s, has been shown to inhibit P-glycoprotein
-mediated cellular efflux. The modulation of P-glycoprotein activity may result in altered absorption and bioavailability of drugs that are P-glycoprotein substrates. It has been reported that silymarin inhibits cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.
of silymarin and silybin were investigated by oral and intravenous route in various animal species. No mortality or any signs of adverse effects were observed after silymarin at oral doses of 20 g/kg in mice and 1 g/kg in dogs. The median lethal dose (LD50) after intravenous infusion values are 400 mg/kg in mice, 385 mg/kg in rats and 140 mg/kg in rabbits and dogs. These data demonstrate that the acute toxicity of silymarin is very low.
Similarly, its subacute and chronic toxicity
are very low; the compound is also devoid of embryotoxic potential.
Lab experiments on mice showed that Silibinin protects the hepatic cells against a-amanitin compound found in Amanita Phalloides mushroom poisoning.
Flavonolignan
-Examples:Flavonolignans identified in Silybum marianum silymarin complex include silibinin, silychristin, silydianin, dehydrosilybin, deoxysilycistin, deoxysilydianin, silandrin, silybinome, silyhermin and neosilyhermin and can be produced in vitro. Silibinin is found in the roots of S...
s consisting of among others of silibinin
Silibinin
Silibinin , also known as silybin, is the major active constituent of silymarin, standardized extract of the milk thistle seeds, containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin and silidianin. Silibinin itself is mixture of two diastereomers...
, isosilibinin, silicristin and silidianin. Silibinin itself is mixture of two diastereomer
Diastereomer
Diastereomers are stereoisomers that are not enantiomers.Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are not mirror images of each other.When two diastereoisomers differ from each other at...
s Silibinin A and Silybinin B in approximately equimolar ratio. Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins. Silibinin has also demonstrated anti-cancer effects against human prostate adenocarcinoma cells, estrogen-dependent and -independent human breast carcinoma cells, human ectocervical carcinoma cells, human colon cancer cells, and both small and nonsmall human lung carcinoma cells.
Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (trade name Legalon SIL) a solution for injection
Injection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
, is used in treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning. There is also clinical evidence for the use of silibinin as a supportive element in alcoholic and grade Child ‘A’ liver cirrhosis.
Pharmacology
Poor water solubility and bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
of silymarin led to the development of enhanced formulations. Silipide (trade name Siliphos), a complex of silymarin and phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...
(lecithin), is about ten times more bioavailable than silymarin. It has been also reported that silymarin inclusion complex with β-cyclodextrin
Cyclodextrin
Cyclodextrins are a family of compounds made up of sugar molecules bound together in a ring ....
is much more soluble than silymarin itself. There have also been prepared glycoside
Glycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme...
s of silybin, which show better water solubility and even stronger hepatoprotective effect.
Silymarin, as other flavonoid
Flavonoid
Flavonoids , are a class of plant secondary metabolites....
s, has been shown to inhibit P-glycoprotein
P-glycoprotein
P-glycoprotein 1 also known as multidrug resistance protein 1 or ATP-binding cassette sub-family B member 1 or cluster of differentiation 243 is a glycoprotein that in humans is encoded by the ABCB1 gene...
-mediated cellular efflux. The modulation of P-glycoprotein activity may result in altered absorption and bioavailability of drugs that are P-glycoprotein substrates. It has been reported that silymarin inhibits cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.
Toxicity
The acute toxicityAcute toxicity
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short space of time...
of silymarin and silybin were investigated by oral and intravenous route in various animal species. No mortality or any signs of adverse effects were observed after silymarin at oral doses of 20 g/kg in mice and 1 g/kg in dogs. The median lethal dose (LD50) after intravenous infusion values are 400 mg/kg in mice, 385 mg/kg in rats and 140 mg/kg in rabbits and dogs. These data demonstrate that the acute toxicity of silymarin is very low.
Similarly, its subacute and chronic toxicity
Chronic toxicity
Chronic toxicity is a property of a substance that has toxic effects on a living organism, when that organism is exposed to the substance continuously or repeatedly. Compared with acute toxicity.Two distinct situations need to be considered:...
are very low; the compound is also devoid of embryotoxic potential.
Complementary and alternative medicine
A recent study suggested that silymarin may help patients with type II diabetes by assisting in blood sugar control.Lab experiments on mice showed that Silibinin protects the hepatic cells against a-amanitin compound found in Amanita Phalloides mushroom poisoning.