Silibinin A and silibinin B structures
|AHFS/Drugs.com||International Drug Names|
|Oral and Intravenous|
|Chemical and physical data|
|Molar mass||482.44 g/mol g·mol−1|
|3D model (JSmol)|
|(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 a 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 – not to be confused with water treatment compound of same name, a glass-like Polyphosphate containing Sodium, Calcium Magnesium and Silicate, formulated for the treatment of water problems), 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.[non-primary source needed] 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, like 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.
For approved drug preparations and parenteral applications in the treatment of Amanita mushroom poisoning, the water-soluble silibinin-C-2’,3-dihyrogensuccinate disodium salt is used. In 2011, the same compound also received Orphan Medicinal Product Designation for the prevention of recurrent hepatitis C in liver transplant recipients by the European Commission.
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). Studies on mice demonstrate a significant protection on chronic unpredictable mild stress (CUMS) induced depressive-like behavior on mice and increased cognition in aged rats as a result of consuming silymarin 
- 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” (PDF). Cancer Research. 65 (10): 4448–57. doi:10.1158/0008-5472.CAN-04-4662. PMID 15899838.
- Saller R, Brignoli R, Melzer J, Meier R (2008). “An updated systematic review with meta-analysis for the clinical evidence of silymarin”. Forschende Komplementärmedizin. 15 (1): 9–20. doi:10.1159/000113648. PMID 18334810. Retrieved 2010-12-14.
- Kidd P, Head K (2005). “A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos)” (PDF). Alternative Medicine Review. 10 (3): 193–203. PMID 16164374. Archived from the original (PDF) on 2011-07-28. Retrieved 2010-12-14.
- Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E (1990). “Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects”. Eur J Drug Metab Pharmacokinet. 15 (4): 333–8. doi:10.1007/bf03190223. PMID 2088770.
- Voinovich D, Perissutti B, Grassi M, Passerini N, Bigotto A (2009). “Solid state mechanochemical activation of Silybum marianum dry extract with betacyclodextrins: Characterization and bioavailability of the coground systems”. Journal of Pharmaceutical Sciences. 98 (11): 4119–29. doi:10.1002/jps.21704. PMID 19226635.
- Kosina P, Kren V, Gebhardt R, Grambal F, Ulrichová J, Walterová D (2002). “Antioxidant properties of silybin glycosides”. Phytotherapy Research. 16 Suppl 1: S33–9. doi:10.1002/ptr.796. PMID 11933137.
- Zhou S, Lim LY, Chowbay B (2004). “Herbal modulation of P-glycoprotein”. Drug Metabolism Reviews. 36 (1): 57–104. doi:10.1081/DMR-120028427. PMID 15072439.
- Wu JW, Lin LC, Tsai TH (2009). “Drug-drug interactions of silymarin on the perspective of pharmacokinetics”. Journal of Ethnopharmacology. 121 (2): 185–93. doi:10.1016/j.jep.2008.10.036. PMID 19041708. Retrieved 2010-12-14.
- 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. PMID 17077998.
- Fraschini F, Demartini G, Esposti D (2002). “Pharmacology of Silymarin”. Clinical Drug Investigation. 22 (1): 51–65. doi:10.2165/00044011-200222010-00007. Archived from the original on 2012-10-27.
- Hahn G, Lehmann HD, Kürten M, Uebel H, Vogel G (1968). “On the pharmacology and toxicology of silymarin, an antihepatotoxic active principle from Silybum marianum (L.) gaertn”. Arzneimittelforschung. 18 (6): 698–704. PMID 5755807.
- Rottapharm|Madaus. Media Communications Legalon®. Retrieved March 6, 2017.
- Bosch-Barrera, Joaquim; Sais, Elia; Cañete, Noemí; Marruecos, Jordi; Cuyàs, Elisabet; Izquierdo, Angel; Porta, Rut; Haro, Manel; Brunet, Joan; Pedraza, Salvador; Menendez, Javier A. (2016). “Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin”. Oncotarget. 7 (22): 32006–32014. doi:10.18632/oncotarget.7900. PMC 5077992. PMID 26959886.
- 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 2767273. PMID 19695480.
- Thakare, Vishnu N; Patil, Rajesh R; Oswal, Rajesh J; Dhakane, Valmik D; Aswar, Manoj K; Patel, Bhoomika M (February 2018). “Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice”. Journal of Psychopharmacology. 32 (2): 223–235. doi:10.1177/0269881117742666. ISSN 0269-8811. PMID 29215318.
- Sarubbo, F.; Ramis, M. R.; Kienzer, C.; Aparicio, S.; Esteban, S.; Miralles, A.; Moranta, D. (March 2018). “Chronic Silymarin, Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats”. Journal of Neuroimmune Pharmacology. 13 (1): 24–38. doi:10.1007/s11481-017-9759-0. ISSN 1557-1890. PMID 28808887.
- 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. PMC 6256978. PMID 20110894.
- 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)