Silymarin for HCV infection

Antiviral Therapy

Volumn 18, Issue 2, 2013, Pages 141-147

  Polyak, Stephen J ^a   Oberlies, Nicholas H ^b   Pécheur, Eve Isabelle ^c   Dahari, Harel ^d,e,f   Ferenci, Peter ^g   Pawlotsky, Jean Michel ^h,i  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

^c CENTRE DE RECHERCHE EN CANCÉROLOGIE DE LYON   (France)

^d UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^e LOS ALAMOS NATIONAL LABORATORY   (United States)

^f LOYOLA UNIVERSITY CHICAGO   (United States)

^g MEDICAL UNIVERSITY OF VIENNA   (Austria)

^h UNIVERSITÉ PARIS EST CRÉTEIL   (France)

ⁱ INSERM U955   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALPHA INTERFERON; ANTIVIRUS AGENT; DISUCCINYL SILYBIN A; DISUCCINYL SILYBIN B; FLAVONOLIGNAN; ISOSILYBIN A; ISOSILYBIN B; ISOSILYCHRISTIN; NONSTRUCTURAL PROTEIN 5B; PLACEBO; SILIBININ; SILIBININ A; SILIBININ B; SILIBININ PHOSPHATIDYLCHOLINE COMPLEX; SILICRISTIN; SILIDIANIN; SILYMARIN; UNCLASSIFIED DRUG; VIRUS RNA;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIVIRAL ACTIVITY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG EFFICACY; DRUG MEGADOSE; DRUG METABOLISM; DRUG PURITY; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; ENZYME INHIBITION; GRAFT INFECTION; HEPATITIS C; HOST PATHOGEN INTERACTION; HUMAN; IC 50; IN VITRO STUDY; INFECTION PREVENTION; LIVER PROTECTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; TREATMENT DURATION; VIRUS ENTRY; VIRUS INHIBITION; VIRUS LOAD; VIRUS REPLICATION;

ANIMALS; ANTIVIRAL AGENTS; HEPACIVIRUS; HEPATITIS C; HUMANS; SILYMARIN;

EID: 84875679143     PISSN: 13596535     EISSN: 20402058     Source Type: Journal    
DOI: 10.3851/IMP2402     Document Type: Review

References (46)

1. Ramasamy K, Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett 2008; 269:352-362.
2. Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DY. Inhibition of T-cell inlammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. Gastroenterology 2007; 132:1925-1936.
3. Wagoner J, Negash A, Kane OJ, et al. Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology 2010; 51:1912-1921.
4. Ferenci P, Scherzer TM, Kerschner H, et al. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 2008; 135:1561-1567.
5. Beinhardt S, Rasoul-Rockenschaub S, Scherzer TM, Ferenci P. Silibinin monotherapy prevents graft infection after orthotopic liver transplantation in a patient with chronic hepatitis C. J Hepatol 2011; 54:591-592.
6. Eurich D, Bahra M, Berg T, et al. Treatment of hepatitis C-virus-reinfection after liver transplant with silibinin in nonresponders to pegylated interferon-based therapy. Exp Clin Transplant 2011; 9:1-6.
7. Neumann UP, Biermer M, Eurich D, Neuhaus P, Berg T. Successful prevention of hepatitis C virus (HCV) liver graft reinfection by silibinin mono-therapy. J Hepatol 2010; 52:951-952.
8. Hawke RL, Schrieber SJ, Soule TA, et al. Silymarin ascending multiple oral dosing Phase I study in noncirrhotic patients with chronic hepatitis C. J Clin Pharmacol 2010; 50:434-449.
9. Graf TN, Wani MC, Agarwal R, Kroll DJ, Oberlies NH. Gram-scale puriication of lavonolignan diastereoisomers from Silybum marianum (milk thistle) extract in support of preclinical in vivo studies for prostate cancer chemoprevention. Planta Med 2007; 73:1495-1501.
10. Kroll DJ, Shaw HS, Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther 2007; 6:110-119.
11. Kiesewetter E, Leodolter I, Thaler H. [Results of two doubleblind studies on the effect of silymarine in chronic hepatitis]. Leber Magen Darm 1977; 7:318-323. German.
12. Marcelli R, Bizzoni P, Conte D, et al. Randomized controlled study of the eficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. European Bulletin of Drug Research 1992; 1:131-135.
13. Buzzelli G, Moscarella S, Giusti A, Duchini A, Marena C, Lampertico M. A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol 1993; 31:456-460.
14. Tanamly MD, Tadros F, Labeeb S, et al. Randomised doubleblinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis 2004; 36:752-759.
15. Huber R, Futter I, Ludtke R. Oral silymarin for chronic hepatitis C -a retrospective analysis comparing three dose regimens. Eur J Med Res 2005; 10:68-70.
16. Melhem A, Stern M, Shibolet O, et al. Treatment of chronic hepatitis C virus infection via antioxidants: results of a Phase I clinical trial. J Clin Gastroenterol 2005; 39:737-742.
17. Gordon A, Hobbs DA, Bowden DS, et al. Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C. J Gastroenterol Hepatol 2006; 21:275-280.
18. Seeff LB, Curto TM, Szabo G, et al. Herbal product use by persons enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Hepatology 2008; 47:605-612.
19. Freedman ND, Curto TM, Morishima C, et al. Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. Aliment Pharmacol Ther 2011; 33:127-137.
20. Rutter K, Scherzer TM, Beinhardt S, et al. Intravenous silibinin as 'rescue treatment' for on-treatment non-responders to pegylated interferon/ribavirin combination therapy. Antivir Ther 2011; 16:1327-1333.
21. Biermer M, Schlosser B, Fulop F, et al. High-dose silibinin rescue treatment for HCV-infected patients showing suboptimal virologic response to standard combination therapy. J Viral Hepat 2012; 19:547-553.
22. Ahmed-Belkacem A, Ahnou N, Barbotte L, et al. Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Gastroenterology 2010; 138:1112-1122.
23. Morishima C, Shuhart MC, Wang CC, et al. Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection. Gastroenterology 2010; 138:671-681.
24. Wagoner J, Morishima C, Graf TN, et al. Differential in vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inlammation. PLoS ONE 2011; 6:e16464.
25. György I, Antus S, Blazovics A, Foldiak G. Substituent effects in the free radical reactions of silybin: radiation-induced oxidation of the lavonoid at neutral pH. Int J Radiat Biol 1992; 61:603-609.
26. Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral eficacy of interferon-alpha therapy. Science 1998; 282:103-107.
27. Dahari H, Guedj J, Perelson AS, Layden TJ. Hepatitis C viral kinetics in the era of direct acting antiviral agents and IL28B. Curr Hepat Rep 2011; 10:214-227.
28. Guedj J, Dahari H, Pohl RT, Ferenci P, Perelson AS. Understanding silibinin's modes of action against HCV using viral kinetic modeling. J Hepatol 2012; 56:1019-1024.
29. Polyak SJ, Morishima C, Lohmann V, et al. Identiication of hepatoprotective lavonolignans from silymarin. Proc Natl Acad Sci U S A 2010; 107:5995-5999.
30. Dahari H, Guedj J, Perelson AS. Silibinin mode of action against hepatitis C virus: a controversy yet to be resolved. Hepatology 2011; 54:749.
31. Schrieber SJ, Hawke RL, Wen Z, et al. Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C. Drug Metab Dispos 2011; 39:2182-2190.
32. Schrieber SJ, Wen Z, Vourvahis M, et al. The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic fatty liver disease and correlates with plasma caspase-3/7 activity. Drug Metab Dispos 2008; 36:1909-1916.
33. Wen Z, Dumas TE, Schrieber SJ, Hawke RL, Fried MW, Smith PC. Pharmacokinetics and metabolic proile of free, conjugated, and total silymarin lavonolignans in human plasma after oral administration of milk thistle extract. Drug Metab Dispos 2008; 36:65-72.
34. Weyhenmeyer R, Mascher H, Birkmayer J. Study on doselinearity of the pharmacokinetics of silibinin diastereomers using a new stereospeciic assay. Int J Clin Pharmacol Ther Toxicol 1992; 30:134-138.
35. Rickling B, Hans B, Kramarczyk R, Krumbiegel G, Weyhenmeyer R. Two high-performance liquid chromatographic assays for the determination of free and total silibinin diastereomers in plasma using column switching with electrochemical detection and reversed-phase chromatography with ultraviolet detection. J Chromatogr B Biomed Appl 1995; 670:267-277.
36. Gatti G, Perucca E. Plasma concentrations of free and conjugated silybin after oral intake of a silybinphosphatidylcholine complex (silipide) in healthy volunteers. Int J Clin Pharmacol Ther 1994; 32:614-617.
37. Lorenz D, Lucker PW, Mennicke WH, Wetzelsberger N. studies with silymarin in human serum and bile. Methods Find Exp Clin Pharmacol 1984; 6:655-661.
38. Schrieber SJ, Wen Z, Vourvahis M, et al. Silymarin pharmacokinetics (PK) is altered in patients with chronic hepatitis C virus (HCV) and nonalcoholic fatty liver disease (NAFLD) and correlates with caspase-3/7 activity. Hepatology 2007; 46:807A.
39. Flaig TW, Gustafson DL, Su LJ, et al. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs 2007; 25:139-146.
40. Fried MW, Navarro VJ, Afdhal N, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA 2012; 308:274-282.
41. Reddy KR, Belle SH, Fried MW, et al. Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C. Clin Trials 2012; 9:102-112.
42. Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol 2009; 121:185-193.
43. Esser-Nobis K, Romero-Brey I, Ganten T, et al. Analysis of hepatitis C virus resistance to Silibinin in vitro and in vivo points to a novel mechanism involving nonstructural protein 4B. Hepatology 2013; doi: 10.1002/hep.26260.
44. McClure J, Lovelace ES, Elahi S, et al. Silibinin inhibits HIV-1 infection by reducing cellular activation and proliferation. PLoS ONE 2012; 7:e41832.
45. Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res 2010; 24:1423-1432.
46. Comelli MC, Mengs U, Schneider C, Prosdocimi M. Toward the deinition of the mechanism of action of silymarin: activities related to cellular protection from toxic damage induced by chemotherapy. Integr Cancer Ther 2007; 6:120-129.