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词条 Silibinin
释义

  1. Pharmacology

  2. Toxicity

  3. Medical uses

  4. Potential medical uses

  5. Biotechnology

  6. References

  7. External links

{{primary sources|date=February 2019}}{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464390273
| 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
| image = Silibinin A.svg
| image2 = Silibinin B.svg
| caption = Silibinin A and silibinin B structures
| tradename =
| Drugs.com = {{drugs.com|international|silibinin}}
| routes_of_administration = Oral and Intravenous
| 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
| C=25 | H=22 | O=10
| molecular_weight = 482.44 g/mol
| smiles = O=C4c5c(O)cc(O)cc5O[C@H](c2ccc1O[C@@H]([C@H](Oc1c2)c3ccc(O)c(OC)c3)CO)[C@H]4O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = SEBFKMXJBCUCAI-HKTJVKLFSA-N
}}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.[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

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.[2]{{primary source inline|date=February 2019}} 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, like 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]

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.[3]

Silymarin is also devoid of embryotoxic potential in animal models.[10][11]

Medical uses

{{main|Silybum marianum#Research}}

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.{{Citation needed|date=July 2018}}

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.[4]

Potential medical uses

Silibinin is under investigation to see whether it may have a role in cancer treatment (e.g. due to its inhibition of STAT3 signalling).[5]

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).[6] Studies on mice demonstrate a significant protection on chronic unpredictable mild stress (CUMS) induced depressive-like behavior on mice[7] and increased cognition in aged rats as a result of consuming silymarin [8]

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.[9]

References

1. ^{{cite journal | vauthors = Davis-Searles P, Nakanishi Y, Nam-Cheol K et al | year = 2005 | title = Milk Thistle and Prostate Cancer: Differential Effects of Pure Flavonolignans from Silybum marianum on Antiproliferative End Points in Human Prostate Carcinoma Cells | url = http://cancerres.aacrjournals.org/content/canres/65/10/4448.full.pdf| journal = Cancer Research | volume = 65 | issue = 10| pages = 4448–57 | doi = 10.1158/0008-5472.CAN-04-4662 | pmid=15899838}}
2. ^{{cite journal | vauthors = Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E | year = 1990 | title = Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects| pmid = 2088770| journal = Eur J Drug Metab Pharmacokinet | volume = 15 | issue = 4| pages = 333–8 | doi=10.1007/bf03190223}}
3. ^{{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 |author1=Thomas W. Flaig |author2=Daniel L. Gustafson |author3=Lih-Jen Su |author4=Joseph A. Zirrolli |author5=Frances Crighton |author6=Gail S. Harrison |author7=A. Scott Pierson |author8=Rajesh Agarwal |author9=L. Michael Glodé | doi=10.1007/s10637-006-9019-2| pmid = 17077998 }}
4. ^Rottapharm|Madaus. Media Communications Legalon®. Retrieved March 6, 2017.
5. ^{{cite journal|first1=Joaquim|last1=Bosch-Barrera|first2=Elia|last2=Sais|first3=Noemí|last3=Cañete|first4=Jordi|last4=Marruecos|title=Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin|journal=Oncotarget|pages=32006–32014|volume=7|issue=22|doi=10.18632/oncotarget.7900|pmid=26959886|first5=Elisabet|last5=Cuyàs|first6=Angel|last6=Izquierdo|first7=Rut|last7=Porta|first8=Manel|last8=Haro|first9=Joan|last9=Brunet|first10=Salvador|last10=Pedraza|first11=Javier A.|last11=Menendez|doi-access=free|pmc=5077992|year=2016}}
6. ^{{cite journal|last1=Singh|first1=Rana P.|last2=Agarwal|first2=Rajesh|title=Cosmeceuticals and silibinin|journal=Clinics in Dermatology|date=September 2009|volume=27|issue=5|pages=479–484|doi=10.1016/j.clindermatol.2009.05.012|pmid=19695480|pmc=2767273}}
7. ^{{Cite journal|last=Thakare|first=Vishnu N|last2=Patil|first2=Rajesh R|last3=Oswal|first3=Rajesh J|last4=Dhakane|first4=Valmik D|last5=Aswar|first5=Manoj K|last6=Patel|first6=Bhoomika M|date=February 2018|title=Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice|journal=Journal of Psychopharmacology|volume=32|issue=2|pages=223–235|doi=10.1177/0269881117742666|pmid=29215318|issn=0269-8811}}
8. ^{{Cite journal|last=Sarubbo|first=F.|last2=Ramis|first2=M. R.|last3=Kienzer|first3=C.|last4=Aparicio|first4=S.|last5=Esteban|first5=S.|last6=Miralles|first6=A.|last7=Moranta|first7=D.|date=March 2018|title=Chronic Silymarin, Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats|journal=Journal of Neuroimmune Pharmacology|volume=13|issue=1|pages=24–38|doi=10.1007/s11481-017-9759-0|pmid=28808887|issn=1557-1890}}
9. ^{{cite journal | vauthors = Tůmová L, Tůma J, Megušar K, Doleža M | year = 2010 | title = Substituted Pyrazinecarboxamides as Abiotic Elicitors of Flavolignan Production in Silybum marianum (L.) Gaertn Cultures in Vitro | url = | journal = Molecules | volume = 15 | issue = 1| pages = 331–340 | doi = 10.3390/molecules15010331 | pmid = 20110894 | pmc = 6256978 }}
10. ^1 {{cite journal |vauthors=Kosina P, Kren V, Gebhardt R, Grambal F, Ulrichová J, Walterová D |title=Antioxidant properties of silybin glycosides |journal=Phytotherapy Research |volume=16 Suppl 1 |issue= |pages=S33–9 |year=2002 |pmid=11933137 |doi= 10.1002/ptr.796}}
11. ^1 {{cite journal |vauthors=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 |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}}
12. ^1 {{cite journal |vauthors=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}}
13. ^1 {{cite journal |vauthors=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}}
14. ^1 {{cite journal |vauthors=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 }}
15. ^1 {{cite journal |vauthors=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 |deadurl=yes |archiveurl=https://web.archive.org/web/20121027121930/http://adisonline.com/druginvestigation/Abstract/2002/22010/Pharmacology_of_Silymarin.7.aspx |archivedate=2012-10-27 }}
16. ^1 {{cite journal |vauthors=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 }}
[10][11][12][13][14][15][16]
}}

External links

  • Review of the Quality of Evidence for Milk Thistle Use from MayoClinic.com
  • {{cite journal |vauthors=Morazzoni P, Bombardelli E |title=Silybum marianum (cardus marianus) |journal=Fitoterapia |volume=66 |pages=3–42 |year=1994}}
  • {{cite journal |vauthors=Saller R, Meier R, Brignoli R |title=The use of silymarin in the treatment of liver diseases |journal=Drugs |volume=61 |issue=14 |pages=2035–63 |year=2001 |pmid=11735632 |doi=10.2165/00003495-200161140-00003 }}
  • {{MeshName|Silymarin}}
{{Bile and liver therapy}}{{lignan}}

3 : Antidotes|Flavonolignans|Phenols
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