Submitted by: Submitted by

Views: 135

Words: 5512

Pages: 23

Category: Business and Industry

Date Submitted: 05/27/2013 10:17 PM

Report This Essay

Identification of hepatoprotective flavonolignans from silymarin

Stephen J. Polyaka,b,c,1, Chihiro Morishimaa, Volker Lohmannd, Sampa Pala, David Y. W. Leee, Yanze Liue, Tyler N. Graf f, and Nicholas H. Oberliesf

Departments of aLaboratory Medicine, bMicrobiology and cGlobal Health, University of Washington, Seattle, WA 98104; dDepartment of Molecular Virology, University of Heidelberg, 69120 Heidelberg, Germany; eBio-Organic and Natural Products Laboratory, McLean Hospital, Belmont, MA 02478; and fDepartment of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402 Edited* by Harvey J. Alter, The Warren G. Magnuson Clinical Center, Bethesda, MD, and approved February 22, 2010 (received for review December 11, 2009)

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-α-induced NF-κB transcription, virus-induced oxidative stress, and T-cell proliferation. All compounds were well tolerated by Huh7 human hepatoma cells up to 80 μM, except for isosilybin B, which was toxic to cells above 10 μM. 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 μM. Silymarin suppressed TNF-α activation of NF-κB dependent transcription, which involved partial inhibition of IκB 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...

More like this