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Carcinogenesis Advance Access published online on September 18, 2008
Carcinogenesis, doi:10.1093/carcin/bgn211
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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American ginseng suppresses inflammation and DNA damage associated with mouse colitis

Yu Jin1,**, Venkata S. Kotakadi1,**, Lei Ying1, Anne B. Hofseth1, Xiangli Cui1, Patricia A. Wood2, Anthony Windust3, Lydia E. Matesic4, Edsel A. Pena5, Codruta Chiuzan5, Narendra P. Singh6, Mitzi Nagarkatti6, Prakash S. Nagarkatti6, Michael J. Wargovich7 and Lorne J. Hofseth1,*

1 Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, SC 29208
2 WJB Dorn VA Medical Center and the School of Medicine, University of South Carolina, Columbia, SC 29209
3 Institute for National Measurement Standards, National Research Council, Ottawa, Canada
4 Department of Biological Sciences, University of South Carolina, Columbia, SC 29208
5 Department of Statistics, University of South Carolina, Columbia, SC 29208
6 Pathology and Microbiology, School of Medicine, University of South Carolina, Columbia, SC 29208
7 Cell and Molecular Pharmacology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425

* Address request for reprints: Lorne J. Hofseth, Ph.D., Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, 770 Sumter St., Coker Life Sciences, Rm. 513C, University of South Carolina, Columbia, SC 29208, Ph. 803-777-6627 (Office). 803-777-2080 (Lab). Fax: 803-777-8356. Email: hofseth{at}cop.sc.edu.

Ulcerative colitis (UC) is a dynamic, idiopathic, chronic inflammatory condition associated with a high colon cancer risk. American ginseng has anti-oxidant properties, and targets many of the players in inflammation. The aim of this study was to test whether American ginseng extract prevents and treats colitis. Colitis in mice was induced by the presence of 1% dextran sulfate sodium (DSS) in the drinking water, or by 1% oxazolone rectally. American ginseng extract was mixed in the chow at levels consistent with that currently consumed by humans as a supplement (75 ppm, equivalent to 58 mg daily). To test prevention of colitis, American ginseng extract was given prior to colitis induction. To test treatment of colitis, American ginseng extract was given after the onset of colitis. In vitro studies were performed to examine mechanisms. Results indicate that American ginseng extract not only prevents, but it treats colitis. iNOS and Cox-2 (markers of inflammation) and p53 (induced by inflammatory stress) are also down-regulated by American ginseng. Mucosal and DNA damage associated with colitis is at least in part a result of an oxidative burst from overactive leukocytes. We therefore tested the hypothesis that American ginseng extract can inhibit leukocyte activation, and subsequent epithelial cell DNA damage in vitro and in vivo. Results are consistent with this hypothesis. The use of American ginseng extract represents a novel therapeutic approach for the prevention and treatment of UC.

Key Words: Inflammation • Cancer • Ginseng • Colitis • Oxidative Stress

** These authors contributed equally to this work

Received June 19, 2008; revised July 28, 2008; accepted September 3, 2008.


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