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Carcinogenesis Advance Access originally published online on June 20, 2008
Carcinogenesis 2008 29(9):1799-1806; doi:10.1093/carcin/bgn143
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis

Venkata S. Kotakadi{dagger}, Yu Jin{dagger}, Anne B. Hofseth, Lei Ying, Xiangli Cui, Suresh Volate, Alexander Chumanevich, Patricia A. Wood1, Robert L. Price2, Anna McNeal2, Udai P. Singh2, Narendra P. Singh2, Mitzi Nagarkatti2, Prakash S. Nagarkatti2, Lydia E. Matesic3, Karine Auclair4, Michael J. Wargovich5 and Lorne J. Hofseth*

Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
1 William Jenning Bryan Dorn VA Medical Center and the School of Medicine, University of South Carolina, Columbia, SC 29209, USA
2 Department of Pathology and Microbiology, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
3 Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
4 Department of Chemistry, McGill University, Montréal, Québec H3A 2K6, Canada
5 Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29425, USA

* To whom correspondence should be addressed. Department of Biomedical and Pharmaceutical Sciences, South Carolina College of Pharmacy, 770 Sumter Street, Coker Life Sciences, Room 513C, University of South Carolina, Columbia, SC 29208, USA. Tel: +1 803 777 6627; Fax: +1 803 777 8356; Email: hofseth{at}cop.sc.edu

Ulcerative colitis is a dynamic, chronic inflammatory condition of the colon associated with an increased colon cancer risk. Ginkgo biloba is a putative antioxidant and has been used for thousands of years to treat a variety of ailments. The aim of this study was to test whether the standardized G.biloba extract, EGb 761, is an antioxidant that can be used to prevent and treat colitis in mice. Here, we show that EGb 761 suppresses the activation of macrophages and can be used to both prevent and treat mouse colitis. Markers of inflammation (iNOS, Cox-2 and tumor necrosis factor-{alpha}) and inflammatory stress (p53 and p53-phospho-serine 15) are also downregulated by EGb 761. Furthermore, we show that EGb 761 reduces the numbers of CD4+/CD25–/Foxp3– effector T cells in the colon. Interestingly, EGb 761 drives CD4+ effector T cell apoptosis in vitro and in vivo, providing a mechanistic explanation to the reduction in numbers of this cell type in the colon. This current study is in agreement with previous studies supporting a use of EGb 761 as a complementary and alternative strategy to abate colitis and associated colon cancer.

Abbreviations: DSS, dextran sulfate sodium; IBD, inflammatory bowel disease; IFN-{gamma}, interferon-{gamma}; PBS, phosphate-buffered saline; TNF-{alpha}, tumor necrosis factor-{alpha}

{dagger} These authors contributed equally to this work.

Received March 10, 2008; revised May 14, 2008; accepted June 6, 2008.


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