Silibinin

Silibinin

File:Silibinin skeletal.svg
File:Silibinin 3D.png
Systematic (IUPAC) name
(2R,3R)-3,5,7-trihydroxy- 2-[(2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl) -2,3-dihydrobenzo[b][1,4]dioxin-6-yl]chroman-4-one
Identifiers
CAS Number	22888-70-6
ATC code	A05BA03 (WHO)
PubChem	CID 31553
Chemical data
Formula	C25H22O10
Molar mass	482.44 g/mol[[]]

Silibinin (INN), also known as silybin, is the major active constituent of silymarin, the mixture of flavonolignans extracted from blessed milk thistle (Silybum marianum) consisting of silibinin A and B, isosibilinin A and B, silicristin, silidianin. 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.

Pharmacology

Poor water solubility and bioavailability 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 glycosides of silybin, which show better water solubility and even stronger hepatoprotective effect.

Silymarin, as other flavonoids, 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 inhibit cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.

Toxicity

The acute toxicity 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 50% 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.

Complementary and alternative medicine

A recent study suggested that silymarin may help patients with type II diabetes by assisting in blood sugar control.

References

• Morazzoni P, Bombardelli E (1994). "Silybum marianum (cardus marianus)". Fitoterapia. 66: 3–42. 
• Saller R, Meier R, Brignoli R (2001). "The use of silymarin in the treatment of liver diseases". Drugs. 61 (14): 2035–63. doi:10.2165/00003495-200161140-00003. PMID 11735632. CS1 maint: Multiple names: authors list (link)

External links

• Review of the Quality of Evidence for Milk Thistle Use from MayoClinic.com
• Intravenous Milk Thistle Compound Used to Save Victims of Poisonous Mushrooms
• MeSH Silymarin

de:Silibinin zh:水飛薊