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Identification of hepatoprotective flavonolignans from silymarin.
Proc Natl Acad Sci U S A. 2010 Mar 30; 107(13):5995-9.PN

Abstract

Silymarin, also known as milk thistle extract, inhibits hepatitis C virus (HCV) infection and also displays antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. In the current study, we evaluated the hepatoprotective actions of the seven major flavonolignans and one flavonoid that comprise silymarin. Activities tested included inhibition of: HCV cell culture infection, NS5B polymerase activity, TNF-alpha-induced NF-kappaB transcription, virus-induced oxidative stress, and T-cell proliferation. All compounds were well tolerated by Huh7 human hepatoma cells up to 80 muM, except for isosilybin B, which was toxic to cells above 10 muM. Select compounds had stronger hepatoprotective functions than silymarin in all assays tested except in T cell proliferation. Pure compounds inhibited JFH-1 NS5B polymerase but only at concentrations above 300 muM. Silymarin suppressed TNF-alpha activation of NF-kappaB dependent transcription, which involved partial inhibition of IkappaB and RelA/p65 serine phosphorylation, and p50 and p65 nuclear translocation, without affecting binding of p50 and p65 to DNA. All compounds blocked JFH-1 virus-induced oxidative stress, including compounds that lacked antiviral activity. The most potent compounds across multiple assays were taxifolin, isosilybin A, silybin A, silybin B, and silibinin, a mixture of silybin A and silybin B. The data suggest that silymarin- and silymarin-derived compounds may influence HCV disease course in some patients. Studies where standardized silymarin is dosed to identify specific clinical endpoints are urgently needed.

Authors+Show Affiliations

Department of Laboratory Medicine, Microbiology and Global Health, University of Washington, Seattle, WA 98104, USA. polyak@u.washington.eduNo 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

Language

eng

PubMed ID

20231449

Citation

Polyak, Stephen J., et al. "Identification of Hepatoprotective Flavonolignans From Silymarin." Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 13, 2010, pp. 5995-9.
Polyak SJ, Morishima C, Lohmann V, et al. Identification of hepatoprotective flavonolignans from silymarin. Proc Natl Acad Sci USA. 2010;107(13):5995-9.
Polyak, S. J., Morishima, C., Lohmann, V., Pal, S., Lee, D. Y., Liu, Y., Graf, T. N., & Oberlies, N. H. (2010). Identification of hepatoprotective flavonolignans from silymarin. Proceedings of the National Academy of Sciences of the United States of America, 107(13), 5995-9. https://doi.org/10.1073/pnas.0914009107
Polyak SJ, et al. Identification of Hepatoprotective Flavonolignans From Silymarin. Proc Natl Acad Sci USA. 2010 Mar 30;107(13):5995-9. PubMed PMID: 20231449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of hepatoprotective flavonolignans from silymarin. AU - Polyak,Stephen J, AU - Morishima,Chihiro, AU - Lohmann,Volker, AU - Pal,Sampa, AU - Lee,David Y W, AU - Liu,Yanze, AU - Graf,Tyler N, AU - Oberlies,Nicholas H, Y1 - 2010/03/15/ PY - 2010/3/17/entrez PY - 2010/3/17/pubmed PY - 2010/4/29/medline SP - 5995 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 107 IS - 13 N2 - Silymarin, also known as milk thistle extract, inhibits hepatitis C virus (HCV) infection and also displays antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. In the current study, we evaluated the hepatoprotective actions of the seven major flavonolignans and one flavonoid that comprise silymarin. Activities tested included inhibition of: HCV cell culture infection, NS5B polymerase activity, TNF-alpha-induced NF-kappaB transcription, virus-induced oxidative stress, and T-cell proliferation. All compounds were well tolerated by Huh7 human hepatoma cells up to 80 muM, except for isosilybin B, which was toxic to cells above 10 muM. Select compounds had stronger hepatoprotective functions than silymarin in all assays tested except in T cell proliferation. Pure compounds inhibited JFH-1 NS5B polymerase but only at concentrations above 300 muM. Silymarin suppressed TNF-alpha activation of NF-kappaB dependent transcription, which involved partial inhibition of IkappaB and RelA/p65 serine phosphorylation, and p50 and p65 nuclear translocation, without affecting binding of p50 and p65 to DNA. All compounds blocked JFH-1 virus-induced oxidative stress, including compounds that lacked antiviral activity. The most potent compounds across multiple assays were taxifolin, isosilybin A, silybin A, silybin B, and silibinin, a mixture of silybin A and silybin B. The data suggest that silymarin- and silymarin-derived compounds may influence HCV disease course in some patients. Studies where standardized silymarin is dosed to identify specific clinical endpoints are urgently needed. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/20231449/Identification_of_hepatoprotective_flavonolignans_from_silymarin_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=20231449 DB - PRIME DP - Unbound Medicine ER -