Hepatitis C virus (HCV) is a global disease of the liver that affects over 170 million people. The only approved treatment for chronic hepatitis C is interferon (IFN) and ribavirin, which only cures about 50% of infected patients. Given the chance of success and significant side effects associated with IFN therapy, many patients consume botanicals such as milk thistle. The active ingredient in milk thistle is Silymarin (SM), which is thought to promote a healthy liver. However, exactly how SM promotes a healthy liver is not known. Furthermore, the botanical industry lacks proper standardization of the source plants and preparation of botanical extracts. We propose to determine how SM promotes a healthy liver, using a carefully standardized and validated preparation of SM. We hypothesize that SM acts as an anti-inflammatory and anti-viral agent to protect the liver from HCV infection. We believe these studies will provide a solid foundation for future clinical trials of SM in patients with chronic hepatitis C. Project Narrative: Chronic hepatitis C is a global disease of the liver that affects over 170 million people. It is caused by a hepatitis C virus (HCV). Treatment options for infected people are limited, expensive, associated with major side effects, and frequently of limited efficacy. This project will investigate the mechanisms of hepatoprotection of the botanical silymarin to provide a rational basis for alternative and complementary medicine approaches to treatment of chronic hepatitis C. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AT002895-01A2
Application #
7384347
Study Section
Special Emphasis Panel (ZAT1-DB (27))
Program Officer
Moen, Laura K
Project Start
2008-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
1
Fiscal Year
2008
Total Cost
$247,685
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Smith, Wesley E; Brownell, Jessica; White, Collin C et al. (2012) In vitro toxicity assessment of amphiphillic polymer-coated CdSe/ZnS quantum dots in two human liver cell models. ACS Nano 6:9475-84
Wagoner, Jessica; Morishima, Chihiro; Graf, Tyler N et al. (2011) Differential in vitro effects of intravenous versus oral formulations of silibinin on the HCV life cycle and inflammation. PLoS One 6:e16464
Wagoner, Jessica; Negash, Amina; Kane, Olivia J et al. (2010) Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology 51:1912-21
Morishima, Chihiro; Shuhart, Margaret C; Wang, Chia C et al. (2010) Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection. Gastroenterology 138:671-81, 681.e1-2
Polyak, Stephen J; Morishima, Chihiro; Lohmann, Volker et al. (2010) Identification of hepatoprotective flavonolignans from silymarin. Proc Natl Acad Sci U S A 107:5995-9
Polyak, Stephen J; Morishima, Chihiro; Hawke, Roy (2008) Antiviral effects of silymarin against hepatitis C: the jury is still out. Hepatology 48:345-6