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Multiple effects of silymarin on the hepatitis C virus lifecycle.
Hepatology. 2010 Jun; 51(6):1912-21.Hep

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.

Authors+Show Affiliations

Department of Laboratory Medicine, University of Washington, Seattle, WA 98104-2499, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

20512985

Citation

Wagoner, Jessica, et al. "Multiple Effects of Silymarin On the Hepatitis C Virus Lifecycle." Hepatology (Baltimore, Md.), vol. 51, no. 6, 2010, pp. 1912-21.
Wagoner J, Negash A, Kane OJ, et al. Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology. 2010;51(6):1912-21.
Wagoner, J., Negash, A., Kane, O. J., Martinez, L. E., Nahmias, Y., Bourne, N., Owen, D. M., Grove, J., Brimacombe, C., McKeating, J. A., Pécheur, E. I., Graf, T. N., Oberlies, N. H., Lohmann, V., Cao, F., Tavis, J. E., & Polyak, S. J. (2010). Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology (Baltimore, Md.), 51(6), 1912-21. https://doi.org/10.1002/hep.23587
Wagoner J, et al. Multiple Effects of Silymarin On the Hepatitis C Virus Lifecycle. Hepatology. 2010;51(6):1912-21. PubMed PMID: 20512985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple effects of silymarin on the hepatitis C virus lifecycle. AU - Wagoner,Jessica, AU - Negash,Amina, AU - Kane,Olivia J, AU - Martinez,Laura E, AU - Nahmias,Yaakov, AU - Bourne,Nigel, AU - Owen,David M, AU - Grove,Joe, AU - Brimacombe,Claire, AU - McKeating,Jane A, AU - Pécheur,Eve-Isabelle, AU - Graf,Tyler N, AU - Oberlies,Nicholas H, AU - Lohmann,Volker, AU - Cao,Feng, AU - Tavis,John E, AU - Polyak,Stephen J, PY - 2010/6/1/entrez PY - 2010/6/1/pubmed PY - 2010/6/18/medline SP - 1912 EP - 21 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 51 IS - 6 N2 - UNLABELLED: 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. SN - 1527-3350 UR - https://www.unboundmedicine.com/medline/citation/20512985/Multiple_effects_of_silymarin_on_the_hepatitis_C_virus_lifecycle_ L2 - https://doi.org/10.1002/hep.23587 DB - PRIME DP - Unbound Medicine ER -