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eCAM Advance Access published online on November 1, 2009
eCAM, doi:10.1093/ecam/nep164
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Antioxidant and Hepatoprotective Effects of Silibinin in a Rat Model of Nonalcoholic Steatohepatitis

Yara Haddad, Diane Vallerand, Antoine Brault and Pierre S. Haddad

Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology and Montreal Diabetes Research Center, Université de Montréal, Montréal and Institute of Nutraceutical and Functional Foods, Laval University, Québec, Canada

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease related to the metabolic syndrome, obesity and diabetes. The rising prevalence of NASH and the lack of efficient treatments have led to the exploration of different therapeutic approaches. Milk thistle (Silibum marianum) is a medicinal plant used for its hepatoprotective properties in chronic liver disease since the 4th century BC. We explored the therapeutic effect of silibinin, the plant's most biologically active extract, in an experimental rat NASH model. A control group was fed a standard liquid diet for 12 weeks. The other groups were fed a high-fat liquid diet for 12 weeks without (NASH) or with simultaneous daily supplement with silibinin–phosphatidylcholine complex (Silibinin 200 mg kg–1) for the last 5 weeks. NASH rats developed all key hallmarks of the pathology. Treatment with silibinin improved liver steatosis and inflammation and decreased NASH-induced lipid peroxidation, plasma insulin and TNF-{alpha}. Silibinin also decreased O2•– release and returned the relative liver weight as well as GSH back to normal. Our results suggest that milk thistle's extract, silibinin, possesses antioxidant, hypoinsulinemic and hepatoprotective properties that act against NASH-induced liver damage. This medicinal herb thus shows promising therapeutic potential for the treatment of NASH.

Keywords: High-fat diet – insulin resistance – milk thistle – NASH – oxidative stress

For reprints and all correspondence: Pierre S. Haddad, Département de Pharmacologie, Pavillon Roger Gaudry, Local R-410, Université de Montréal, 2900 boul. Edouard Montpetit, Montréal, Québec, Canada H3T 1J4. Tel: +1-514-343-6590; Fax: +1-514-343-2291; E-mail: pierre.haddad{at}umontreal.ca

Received June 11, 2009; accepted September 15, 2009


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