Silibinin: Difference between revisions

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Silibinin
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral Intravenous
ATC code	A05BA03 (WHO) ;
Identifiers
	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;
CAS Number	22888-70-6 ;
PubChem CID	31553;
ChemSpider	29263 ;
UNII	4RKY41TBTF;
KEGG	D08515 ;
ChEBI	CHEBI:9144 ;
ChEMBL	ChEMBL9509 ;
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
Formula	C25H22O10
Molar mass	482.44 g/mol
3D model (JSmol)	Interactive image;
	SMILES O=C4c5c(O)cc(O)cc5O[C@H](c2ccc1O[C@@H]([C@H](Oc1c2)c3ccc(O)c(OC)c3)CO)[C@H]4O;
	InChI InChI=1S/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-16-5-3-12(7-18(16)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3/t20-,23+,24-,25-/m1/s1 ; Key:SEBFKMXJBCUCAI-HKTJVKLFSA-N ;
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VisualWikitext

Latest revision as of 16:59, 9 April 2015

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.Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins. 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.

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.There is also clinical evidence for the use of silibinin as a supportive element in alcoholic and child grade 'A' liver cirrhosis.

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. 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 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. 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.

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.

The compound is also devoid of embryotoxic potential in animal models.

Potential medical uses

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

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

@@ Line 1: / Line 1: @@
-{{Drugbox|
+{{Drugbox
-|IUPAC_name = <small>3,5,7-trihydroxy-2-(3-(3-hydroxy-4-methoxyphenyl)-2-<br>(hydroxymethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)chroman-4-one</small>
+| Verifiedfields = changed
-| image = Silibinin skeletal.svg
+| verifiedrevid = 464390273
-| image2 = Silibinin 3D.png
+| IUPAC_name = (2''R'',3''R'')-3,5,7-trihydroxy-<br />2-[(2''R'',3''R'')-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)<br />-2,3-dihydrobenzo[''b''][1,4]dioxin-6-yl]chroman-4-one
-| CAS_number= 22888-70-6
+| image = Silibinin.png
-| ATC_prefix=
+| image2 = Silibinin0.png
-| ATC_suffix=
-| PubChem= 31553
+<!--Clinical data-->
-| DrugBank=
+| tradename =
-| C = 25 |H = 22 |O = 10
+| Drugs.com = {{drugs.com|international|silibinin}}
+| routes_of_administration = [[Oral administration|Oral]] [[Intravenous therapy|Intravenous]]
+<!--Identifiers-->
+| CAS_number_Ref = {{cascite|changed|??}}
+| CAS_number = 22888-70-6
+| ATC_prefix = A05
+| ATC_suffix = BA03
+| PubChem = 31553
+| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
+| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
+| ChemSpiderID = 29263
+| ChEBI_Ref = {{ebicite|changed|EBI}}
+| ChEBI = 9144
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = 4RKY41TBTF
+| KEGG_Ref = {{keggcite|correct|kegg}}
+| KEGG = D08515
+| ChEMBL_Ref = {{ebicite|changed|EBI}}
+| ChEMBL = 9509
+<!--Chemical data-->
+| C=25 | H=22 | O=10
 | molecular_weight = 482.44 g/mol
-| bioavailability=
+| smiles = O=C4c5c(O)cc(O)cc5O[C@H](c2ccc1O[C@@H]([C@H](Oc1c2)c3ccc(O)c(OC)c3)CO)[C@H]4O
-| metabolism =
+| InChI = 1/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-16-5-3-12(7-18(16)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3/t20-,23+,24-,25-/m1/s1
-| elimination_half-life=
+| InChIKey = SEBFKMXJBCUCAI-HKTJVKLFBV
-| excretion =
+| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
-| pregnancy_category =
+| StdInChI = 1S/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-16-5-3-12(7-18(16)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3/t20-,23+,24-,25-/m1/s1
-| legal_status =
+| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
-| routes_of_administration=
+| StdInChIKey = SEBFKMXJBCUCAI-HKTJVKLFSA-N
 }}
-'''Silibinin''' ([[International Nonproprietary Name|INN]], also known as '''silybin''', trade name '''Legalon''') is the major active constituent of '''silymarin''', the mixture of flavonolignans extracted from [[Silybum marianum|blessed milk thistle]] (''Silybum marianum''). It is used in the treatment and prevention of [[liver]] diseases because of its hepatoprotective (antihepatotoxic) properties. Clinical tests have also shown its ability to protect against certain types of [[cancer]] (skin and prostate), probably due to its [[antioxidant]] properties.{{Fact|date=April 2007}}
+__NOTOC__
+{{SI}}
+{{CMG}}
+==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.Both ''in vitro'' and animal research suggest that silibinin has [[hepatoprotective]] (antihepatotoxic) properties that protect liver cells against toxins. 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.
-Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (trade name '''Legalon SIL''') a solution for [[injection (medicine)|injection]], is used in treatment of severe intoxications with hepatotoxic substances, such as [[Amanita phalloides|death cap]] (''Amanita phalloides'') poisoning.
+Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (trade name '''Legalon SIL'''), a solution for [[injection (medicine)|injection]], is currently being tested as a treatment of severe intoxications with hepatotoxic substances, such as [[Amanita phalloides|death cap]] (''Amanita phalloides'') poisoning.There is also clinical evidence for the use of silibinin as a supportive element in alcoholic and child grade 'A' [[liver cirrhosis]].
 ==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 [[glycoside]]s of silybin, which show better water solubility and even stronger hepatoprotective effect.
+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. It has been also reported that silymarin inclusion complex with β-[[cyclodextrin]] is much more soluble than silymarin itself.There have also been prepared [[glycoside]]s of silybin, which show better water solubility and even stronger hepatoprotective effect.
-Silymarin, as other [[flavonoid]]s, has been shown to inhibit P-gp-mediated cellular efflux.{{Fact|date=April 2007}} The modulation of P-gp- activity may result in altered absorption and bioavailability of drugs that are P-gp- substrates. It has been reported that silymarin inhibit cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.{{Fact|date=April 2007}}
+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 [[flavonoid]]s, 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.
 ==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&nbsp;g/kg in dogs. The 50% lethal dose ([[LD50|LD<sub>50</sub>]]) 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.{{Fact|date=April 2007}}
+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.
-==Complementary and alternative medicine==
+The compound is also devoid of embryotoxic potential in animal models.
-Silymarin is among the popular complementary medicine for the treatment of cancer. Its use has included treatment of varicose veins, menstrual problems, depression, and low breast milk production. However, the most valuable use of milk thistle-derived silymarin is as a liver supporter to prevent and treat cirrhosis, chronic hepatitis, and gall bladder problems. A recent study suggested that silymarin may help diabetic patients by assisting in blood sugar control.{{Fact|date=April 2007}}
+== Potential medical uses ==
+A recent study suggested that silymarin may help patients with [[type II diabetes]] by assisting in blood sugar control.
+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 (cell biology)|callus]] and cells suspensions of ''[[Silybum marianum]]'' and substituted [[pyrazinecarboxamide]]s can be used as abiotic [[elicitor]]s of flavolignan production.
 ==References==
-*Morazzoni P., Bombardelli E. (1994). Silybum marianum (cardus marianus) Fitoterapia 66:3-42.
+{{Reflist|2}}
-*Saller R., Meier R., Brignoli R. (2001) The use of silymarin in the treatment of liver diseases. Drugs, 61(14), 2035-63.
-* Huseini, H.F: The Efficacy of Silybum marianum (L.) Gaertn. (Silymarin) in the Treatment of Type II Diabetes: A Randomized, Double-blind, Placebo-controlled, Clinical Trial. ''Phytotherapy Research''.
 [[Category:Antidotes]]
-[[Category:Antioxidants]]
+[[Category:Phenols]]
-[[Category:Flavonoids]]
+[[Category:Drug]]
-[[de:Silibinin]]
-[[zh:水飛薊]]
-{{WikiDoc Help Menu}}
-{{WikiDoc Sources}}

Clinical data


AHFS/Drugs.com	International Drug Names
Routes of administration	Oral Intravenous
ATC code	A05BA03 (WHO)
Identifiers
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
CAS Number	22888-70-6^N
PubChem CID	31553
ChemSpider	29263^Y
UNII	4RKY41TBTF
KEGG	D08515^Y
ChEBI	CHEBI:9144^N
ChEMBL	ChEMBL9509^N
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
Formula	C₂₅H₂₂O₁₀
Molar mass	482.44 g/mol
3D model (JSmol)	Interactive image
SMILES O=C4c5c(O)cc(O)cc5O[C@H](c2ccc1O[C@@H]([C@H](Oc1c2)c3ccc(O)c(OC)c3)CO)[C@H]4O
InChI InChI=1S/C25H22O10/c1-32-17-6-11(2-4-14(17)28)24-20(10-26)33-16-5-3-12(7-18(16)34-24)25-23(31)22(30)21-15(29)8-13(27)9-19(21)35-25/h2-9,20,23-29,31H,10H2,1H3/t20-,23+,24-,25-/m1/s1^Y Key:SEBFKMXJBCUCAI-HKTJVKLFSA-N^Y
^NY (what is this?) (verify)