|AHFS/Drugs.com||International Drug Names|
|Chemical and physical data|
|Molar mass||482.44 g/mol|
|3D model (Jmol)|
|(what is this?)|
Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin, and others. Silibinin itself is mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. The mixture exhibits a number of pharmacological effects, particularly in the liver, and there is some clinical evidence for the use of silibinin as a supportive element in alcoholic and child grade 'A' liver cirrhosis.
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 10 times more bioavailable than silymarin. An earlier study had concluded Siliphos to have 4.6 fold higher bioavailability. 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 inhibits cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.
A phase I clinical trial in humans with prostate cancer designed to study the effects of high dose silibinin found 13 grams daily to be well tolerated in patients with advanced prostate cancer with asymptomatic liver toxicity (hyperbilirubinemia and elevation of alanine aminotransferase) being the most commonly seen adverse event.
Silibinin is available as drug (Legalon® SIL (Madaus) (D, CH, A) and Silimarit® (Bionorica), a Silymarin product) in some EU countries and used in the treatment of toxic liver damage (e.g. IV treatment in case of death cap poisoning); as adjunctive therapy in chronic hepatitis and cirrhosis. See also Silybum marianum#Medicinal use
Potential medical uses
Silibinin also has a number of potential mechanisms that could benefit the skin. These include chemoprotective effects from environmental toxins, anti-inflammatory effects, protection from UV induced photocarcinogenesis, protection from sunburn, protection from UVB-induced epidermal hyperplasia, and DNA repair for UV induced DNA damage (double strand breaks).
- Davis-Searles P, Nakanishi Y, Nam-Cheol K, et al. (2005). "Milk Thistle and Prostate Cancer: Differential Effects of Pure Flavonolignans from Silybum marianum on Antiproliferative End Points in Human Prostate Carcinoma Cells". Cancer Research. 65 (10): 4448–57. doi:10.1158/0008-5472.CAN-04-4662. PMID 15899838.
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- Thomas W. Flaig; Daniel L. Gustafson; Lih-Jen Su; Joseph A. Zirrolli; Frances Crighton; Gail S. Harrison; A. Scott Pierson; Rajesh Agarwal; L. Michael Glodé (2007). "A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients". Investigational New Drugs. 25 (2): 139–146. doi:10.1007/s10637-006-9019-2.
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- Bosch-Barrera J, Menendez JA (2015). "Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy". Cancer Treat. Rev. (Review). 41 (6): 540–6. doi:10.1016/j.ctrv.2015.04.008. PMID 25944486.
- Singh, Rana P.; Agarwal, Rajesh (September 2009). "Cosmeceuticals and silibinin". Clinics in Dermatology. 27 (5): 479–484. doi:10.1016/j.clindermatol.2009.05.012. PMC . PMID 19695480.
- Tůmová L, Tůma J, Megušar K, Doleža M (2010). "Substituted Pyrazinecarboxamides as Abiotic Elicitors of Flavolignan Production in Silybum marianum (L.) Gaertn Cultures in Vitro". Molecules. 15 (1): 331–340. doi:10.3390/molecules15010331.
- Review of the Quality of Evidence for Milk Thistle Use from MayoClinic.com
- 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.
- Silymarin at the US National Library of Medicine Medical Subject Headings (MeSH)