Silibinin

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Silibinin
Silibinin skeletal.svg
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
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration
Oral Intravenous
Identifiers
CAS Number 22888-70-6 N
ATC code A05BA03 (WHO)
PubChem CID 31553
ChemSpider 29263 YesY
UNII 4RKY41TBTF YesY
KEGG D08515 YesY
ChEBI CHEBI:9144 N
ChEMBL CHEMBL9509 N
Chemical data
Formula C25H22O10
Molar mass 482.44 g/mol
 NYesY (what is this?)  (verify)

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.[1] 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.[2]

Pharmacology[edit]

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.[3] An earlier study had concluded Siliphos to have 4.6 fold higher bioavailability.[4] It has been also reported that silymarin inclusion complex with β-cyclodextrin is much more soluble than silymarin itself.[5] There have also been prepared glycosides of silybin, which show better water solubility and even stronger hepatoprotective effect.[6]

Silymarin, as other flavonoids, has been shown to inhibit P-glycoprotein-mediated cellular efflux.[7] 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.[8]

Use of Siliphos in Hard Water Treatment[edit]

3M developed a product using Silphos to bind calcium and magnesium hardness minerals, preventing them from precipitating out of solution and building up on metallic surfaces. The specific purpose of this product is to condition the water supply for tankless water heaters to protect the water system from the buildup in the piping that is heated to very high temperatures within the heater itself. This product has been marketed as a way to avoid installing a whole house water softener to achieve the same effect. In addition, polyphosphates from the siliphide also form a thin protective layer on the pipe wall or metallic surface which helps to eliminate hardness build-up and corrosion.[9]

Toxicity[edit]

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.[10]

Silymarin is also devoid of embryotoxic potential in animal models.[11][12]

Medical uses[edit]

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[edit]

Silibinin is under investigation to see whether it may have a role in cancer treatment (e.g. due to its inhibition of STAT3 signalling).[13]

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).[14]

Biotechnology[edit]

Silymarin can be produced in callus and cells suspensions of Silybum marianum and substituted pyrazinecarboxamides can be used as abiotic elicitors of flavolignan production.[15]

References[edit]

  1. ^ 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
  2. ^ 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. 
  3. ^ 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. Retrieved 2010-12-14. 
  4. ^ Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Eur J Drug Metab Pharmacokinet 1990;15:333–8.
  5. ^ 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. 
  6. ^ Kosina P, Kren V, Gebhardt R, Grambal F, Ulrichová J, Walterová D (2002). "Antioxidant properties of silybin glycosides". Phytotherapy Research : PTR. 16 Suppl 1: S33–9. doi:10.1002/ptr.796. PMID 11933137. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ "AP430SS Scale Inhibition System Specification Sheet" (PDF). 3M Purification Inc. Retrieved March 30, 2016. 
  10. ^ 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. 
  11. ^ Fraschini F, Demartini G, Esposti D (2002). "Pharmacology of Silymarin". Clinical Drug Investigation 22 (1): 51–65. doi:10.2165/00044011-200222010-00007. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ Substituted Pyrazinecarboxamides as Abiotic Elicitors of Flavolignan Production in Silybum marianum (L.) Gaertn Cultures in Vitro. Lenka Tůmová, Jiří Tůma, Klara Megušar, and Martin Doleža, Molecules, 2010, 15(1), pages 331-340, doi:10.3390/molecules15010331

External links[edit]