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__NOTOC__
__NOTOC__
{{SI}}
{{SI}}
{CMG}}
{{CMG}}
==Overview==
==Overview==
'''Silibinin''' ([[International Nonproprietary Name|INN]]), also known as '''silybin '''(both from ''[[Silybum]]'', the [[Genus–differentia definition|generic]] name of the [[plant]] from which it is extracted), is the major active constituent of '''silymarin''', a standardized extract of the [[Silybum marianum|milk thistle]] seeds, containing a mixture of [[flavonolignan]]s consisting of silibinin, [[isosilibinin]], [[silicristin]], [[silidianin]] and others. Silibinin itself is mixture of two [[diastereomer]]s, silybin A and silybin B, in approximately equimolar ratio.<ref>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. [http://cancerres.aacrjournals.org/content/65/10/4448.full.pdf doi:10.1158/0008-5472.CAN-04-4662]</ref> Both ''in vitro'' and animal research suggest that silibinin has [[hepatoprotective]] (antihepatotoxic) properties that protect liver cells against toxins.<ref name=AlAnati2009/><ref name=Jayaraj2007/> Silibinin has also demonstrated ''in vitro'' 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.<ref name=Mokhtari2008/><ref name=Bhatia1999/><ref name=Hogan2007/><ref name=Sharma2003/>
'''Silibinin''' ([[International Nonproprietary Name|INN]]), also known as '''silybin '''(both from ''[[Silybum]]'', the [[Genus–differentia definition|generic]] name of the [[plant]] from which it is extracted), is the major active constituent of '''silymarin''', a standardized extract of the [[Silybum marianum|milk thistle]] seeds, containing a mixture of [[flavonolignan]]s consisting of silibinin, [[isosilibinin]], [[silicristin]], [[silidianin]] and others. Silibinin itself is mixture of two [[diastereomer]]s, silybin A and silybin B, in approximately equimolar ratio.<ref>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. [http://cancerres.aacrjournals.org/content/65/10/4448.full.pdf doi:10.1158/0008-5472.CAN-04-4662]</ref> Both ''in vitro'' and animal research suggest that silibinin has [[hepatoprotective]] (antihepatotoxic) properties that protect liver cells against toxins.<ref name=AlAnati2009/><ref name=Jayaraj2007/> Silibinin has also demonstrated ''in vitro'' 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.<ref name=Mokhtari2008/><ref name=Bhatia1999/><ref name=Hogan2007/><ref name=Sharma2003/>
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==Toxicity==
==Toxicity==
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.<ref>{{cite journal | journal = Investigational New Drugs | year = 2007 | volume = 25 | issue = 2 | pages = 139–146 | title = A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients | author = 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 | doi=10.1007/s10637-006-9019-2}}</ref>
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.<ref>{{cite journal | journal = Investigational New Drugs | year = 2007 | volume = 25 | issue = 2 | pages = 139–146 | title = A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients | author = 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 | doi=10.1007/s10637-006-9019-2}}</ref>


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== Biotechnology ==
== Biotechnology ==
Silymarin can be produced in [[callus (cell biology)|callus]] and cells suspensions of ''[[Silybum marianum]]'' and substituted [[pyrazinecarboxamide]]s can be used as abiotic [[elicitor]]s of flavolignan production.<ref>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}}</ref>
Silymarin can be produced in [[callus (cell biology)|callus]] and cells suspensions of ''[[Silybum marianum]]'' and substituted [[pyrazinecarboxamide]]s can be used as abiotic [[elicitor]]s of flavolignan production.
 
== See also ==
* [[Sulfad]], a drug containing silibinin.
 
== References ==
{{Reflist|refs=
 
<ref name=AlAnati2009>{{cite journal |author=Al-Anati L, Essid E, Reinehr R, Petzinger E |title=Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells |journal=Molecular Nutrition & Food Research |volume=53 |issue=4 |pages=460–6 |year=2009 |pmid=19156713 |doi=10.1002/mnfr.200800110}}</ref>
 
<ref name=Bhatia1999>{{cite journal |author=Bhatia N, Zhao J, Wolf DM, Agarwal R |title=Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin |journal=Cancer Letters |volume=147 |issue=1–2 |pages=77–84 |year=1999 |pmid=10660092 |doi=10.1016/S0304-3835(99)00276-1}}</ref>
 
<ref name=Hogan2007>{{cite journal |author=Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS |title=Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer |journal=Journal of Surgical Research |volume=143 |issue=1 |pages=58–65 |year=2007 |pmid=17950073 |doi=10.1016/j.jss.2007.03.080 |url=http://linkinghub.elsevier.com/retrieve/pii/S0022-4804(07)00241-7}}</ref>
 
<ref name=Huseini2006>{{cite journal |author=Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M |title=The efficacy of ''Silybum marianum'' (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial |journal=Phytotherapy Research |volume=20 |issue=12 |pages=1036–9 |year=2006 |pmid=17072885 |doi=10.1002/ptr.1988}}</ref>
 
<ref name=Jayaraj2007>{{cite journal |author=Jayaraj R, Deb U, Bhaskar AS, Prasad GB, Rao PV |title=Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice |journal=Environmental Toxicology |volume=22 |issue=5 |pages=472–9 |year=2007 |pmid=17696131 |doi=10.1002/tox.20283}}</ref>
 
<ref name=Kidd2005>{{cite journal |author=Kidd P, Head K |title=A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos) |journal=Alternative Medicine Review : a Journal of Clinical Therapeutic |volume=10 |issue=3 |pages=193–203 |year=2005 |pmid=16164374 |doi= |url=http://www.thorne.com/altmedrev/.fulltext/10/3/193.pdf |accessdate=2010-12-14}}</ref>
 
<ref name=Kosina2002>{{cite journal |author=Kosina P, Kren V, Gebhardt R, Grambal F, Ulrichová J, Walterová D |title=Antioxidant properties of silybin glycosides |journal=Phytotherapy Research : PTR |volume=16 Suppl 1 |issue= |pages=S33–9 |year=2002  |pmid=11933137 |doi= 10.1002/ptr.796}}</ref>
 
<ref name=Mitchell2009>{{cite journal |author=Mitchell, T |title=Intravenous Milk thistle (silibinin-legalon) for hepatic failure induced by amatoxin/''Amanita'' mushroom poisoning |journal=(Clinical study) |year=2009 |url=http://clinicaltrials.gov/ct2/show/NCT00915681}}</ref>
 
<ref name=Mokhtari2008>{{cite journal |author=Mokhtari MJ, Motamed N, Shokrgozar MA |title=Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line |journal=Cell Biology International |volume=32 |issue=8 |pages=888–92 |year=2008 |pmid=18538589 |doi=10.1016/j.cellbi.2008.03.019 |url=http://linkinghub.elsevier.com/retrieve/pii/S1065-6995(08)00384-3}}</ref>
 
<ref name=Saller2008>{{cite journal |author=Saller R, Brignoli R, Melzer J, Meier R |title=An updated systematic review with meta-analysis for the clinical evidence of silymarin |journal=Forschende Komplementärmedizin (2006) |volume=15 |issue=1 |pages=9–20 |year=2008 |pmid=18334810 |doi=10.1159/000113648 |url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000113648 |accessdate=2010-12-14}}</ref>
 
<ref name=Sharma2003>{{cite journal |author=Sharma G, Singh RP, Chan DC, Agarwal R |title=Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells |journal=Anticancer Research |volume=23 |issue=3B |pages=2649–55 |year=2003 |pmid=12894553}}</ref>
 
<ref name=Voinovich2009>{{cite journal |author=Voinovich D, Perissutti B, Grassi M, Passerini N, Bigotto A |title=Solid state mechanochemical activation of ''Silybum marianum'' dry extract with betacyclodextrins: Characterization and bioavailability of the coground systems |journal=Journal of Pharmaceutical Sciences |volume=98 |issue=11 |pages=4119–29 |year=2009 |pmid=19226635 |doi=10.1002/jps.21704}}</ref>
 
<ref name=Wu2009>{{cite journal |author=Wu JW, Lin LC, Tsai TH |title=Drug-drug interactions of silymarin on the perspective of pharmacokinetics |journal=Journal of Ethnopharmacology |volume=121 |issue=2 |pages=185–93 |year=2009 |pmid=19041708 |doi=10.1016/j.jep.2008.10.036 |url=http://linkinghub.elsevier.com/retrieve/pii/S0378-8741(08)00621-1 |accessdate=2010-12-14}}</ref>
 
<ref name=Zhou2004>{{cite journal |author=Zhou S, Lim LY, Chowbay B |title=Herbal modulation of P-glycoprotein |journal=Drug Metabolism Reviews |volume=36 |issue=1 |pages=57–104 |year=2004 |pmid=15072439 |doi=10.1081/DMR-120028427 |url=http://www.informapharmascience.com/doi/abs/10.1081/DMR-120028427 }}</ref>
 
<ref name=Fraschini2002>{{cite journal |author=Fraschini F, Demartini G, Esposti D |title=Pharmacology of Silymarin |journal=Clinical Drug Investigation |volume=22 |issue=1 |pages=51–65 |year=2002 |doi=10.2165/00044011-200222010-00007 | url=http://adisonline.com/druginvestigation/Abstract/2002/22010/Pharmacology_of_Silymarin.7.aspx }}</ref>
 
<ref name=Hahn1968>{{cite journal |author=Hahn G, Lehmann HD, Kürten M, Uebel H, Vogel G |title=On the pharmacology and toxicology of silymarin, an antihepatotoxic active principle from Silybum marianum (L.) gaertn |journal=Arzneimittelforschung |volume=18 |issue=6 |pages=698–704 |year=1968 |pmid=5755807 }}</ref>
 
}}


==References==
==References==

Revision as of 16:55, 9 April 2015

Silibinin
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral Intravenous
ATC code
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CAS Number
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KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC25H22O10
Molar mass482.44 g/mol
3D model (JSmol)
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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] Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins.[2][3] Silibinin has also demonstrated in vitro 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.[4][5][6][7]

Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (trade name Legalon SIL), a solution for injection, is currently being tested as a treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning.[8] There is also clinical evidence for the use of silibinin as a supportive element in alcoholic and child grade 'A' liver cirrhosis.[9]

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 10 times more bioavailable than silymarin.[10] An earlier study had concluded Siliphos to have 4.6 fold higher bioavailability.[11] It has been also reported that silymarin inclusion complex with β-cyclodextrin is much more soluble than silymarin itself.[12] There have also been prepared glycosides of silybin, which show better water solubility and even stronger hepatoprotective effect.[13] Silibinin has been reported to exert a neuroprotective effect in mice.[14]

Silymarin is the first ingredient in several products sold as herbal telomerase activators, though the research demonstrating silymarin's effectiveness in this regard is proprietary and unpublished.

Silymarin, as other flavonoids, has been shown to inhibit P-glycoprotein-mediated cellular efflux.[15] 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.[16]

Toxicity

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.[17]

The compound is also devoid of embryotoxic potential in animal models.[18][19]

Potential medical uses

A recent study suggested that silymarin may help patients with type II diabetes by assisting in blood sugar control.[20]

Lab experiments on mice showed that silibinin protects the hepatic cells against the toxin alpha-amanitin which causes Amanita phalloides mushroom poisoning.

Biotechnology

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

References

  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. ↑ Invalid <ref> tag; no text was provided for refs named AlAnati2009
  3. ↑ Invalid <ref> tag; no text was provided for refs named Jayaraj2007
  4. ↑ Invalid <ref> tag; no text was provided for refs named Mokhtari2008
  5. ↑ Invalid <ref> tag; no text was provided for refs named Bhatia1999
  6. ↑ Invalid <ref> tag; no text was provided for refs named Hogan2007
  7. ↑ Invalid <ref> tag; no text was provided for refs named Sharma2003
  8. ↑ Invalid <ref> tag; no text was provided for refs named Mitchell2009
  9. ↑ Invalid <ref> tag; no text was provided for refs named Saller2008
  10. ↑ Invalid <ref> tag; no text was provided for refs named Kidd2005
  11. ↑ Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Eur J Drug Metab Pharmacokinet 1990;15:333–8.
  12. ↑ Invalid <ref> tag; no text was provided for refs named Voinovich2009
  13. ↑ Invalid <ref> tag; no text was provided for refs named Kosina2002
  14. ↑ Tota, S; Kamat, PK; Shukla, R; Nath, C (2011). "Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment". Behavioural Brain Research. 221 (1): 207–15. doi:10.1016/j.bbr.2011.02.041. PMID 21382422.
  15. ↑ Invalid <ref> tag; no text was provided for refs named Zhou2004
  16. ↑ Invalid <ref> tag; no text was provided for refs named Wu2009
  17. ↑ 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.
  18. ↑ Invalid <ref> tag; no text was provided for refs named Fraschini2002
  19. ↑ Invalid <ref> tag; no text was provided for refs named Hahn1968
  20. ↑ Invalid <ref> tag; no text was provided for refs named Huseini2006
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