Multiple effects of silymarin on the hepatitis C virus lifecycle.

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Hepatology. 2010 Jun;51(6):1912-21.

Multiple effects of silymarin on the hepatitis C virus lifecycle.

Wagoner J, Negash A, Kane OJ, ez LE, Nahmias Y, Bourne N, Owen DM, Grove

J, Brimacombe C, McKeating JA, Pécheur EI, Graf TN, Oberlies NH, Lohmann V, Cao

F, Tavis JE, Polyak SJ.

Department of Laboratory Medicine, University of Washington, Seattle, WA

98104-2499, USA.

Abstract

Silymarin, an extract from milk thistle (Silybum marianum), and its purified

flavonolignans have been recently shown to inhibit hepatitis C virus (HCV)

infection, both in vitro and in vivo. In the current study, we further

characterized silymarin's antiviral actions. Silymarin had antiviral effects

against hepatitis C virus cell culture (HCVcc) infection that included

inhibition of virus entry, RNA and protein expression, and infectious virus

production. Silymarin did not block HCVcc binding to cells but inhibited the

entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes.

Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA

polymerase (RdRp) activity at concentrations 5 to 10 times higher than required

for anti-HCVcc effects. Furthermore, silymarin had inefficient activity on the

genotype 1b BK and four 1b RDRPs derived from HCV-infected patients. Moreover,

silymarin did not inhibit HCV replication in five independent genotype 1a, 1b,

and 2a replicon cell lines that did not produce infectious virus. Silymarin

inhibited microsomal triglyceride transfer protein activity, apolipoprotein B

secretion, and infectious virion production into culture supernatants. Silymarin

also blocked cell-to-cell spread of virus. CONCLUSION: Although inhibition of in

vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's

antiviral action appear to include blocking of virus entry and transmission,

possibly by targeting the host cell.

PMID: 20512985 [PubMed - in process]

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