Ulcerative colitis (UC) is a chronic inflammatory condition that is immunologically mediated. Approximately 4[unreadable] million people world-wide have the disease and are at increased colon cancer risk. Conventional treatment[unreadable] of colitis can reduce periods of active disease and help to maintain remission, but these treatments are often[unreadable] associated with side effects and have marginal results. For this reason, many colitis sufferers turn to[unreadable] complementary and alternative treatments in hopes of abating symptoms of active disease. It is estimated[unreadable] that about 50% of UC patients use some form of megavitamin therapy or herbal/dietary supplement. There[unreadable] is, however, no documentation on UC patients taking American ginseng to temper the signs and symptoms[unreadable] of colitis. In the current study, we present exciting data that ginseng inhibits the onset of colitis in two mouse[unreadable] models of colitis as well as preventing colitis-driven colon cancer. This grant aims to understand the[unreadable] mechanisms of this inhibition as a necessary pre-requisite to future human clinical trials. We will test the[unreadable] hypothesis that dietary supplementation with American ginseng inhibits UC-associated inflammation in the[unreadable] colon through mechanisms involving induction of apoptosis in immune cells, altered Th1/Th2 cytokine[unreadable] profiles, and/or changes in immune cell migration and trafficking. Because ginseng also inhibits the colitisto-[unreadable] cancer sequence in our model, we will examine whether it suppresses inflammation-driven DMA damage[unreadable] and protein nitration in colon cells. Because pRb is hyperphosphorylated and inactivated in colitis, we will[unreadable] further examine whether ginseng suppresses pRb hyperphosphorylation through mechanisms involving a[unreadable] decrease in the activation of specific kinase pathways. We will investigate whether ginseng mediates these[unreadable] effects through direct action on the colon cells and/or on immune cells. Finally, we propose to delineate the[unreadable] active ingredients of American ginseng responsible for the inhibition of colitis. Together, this study will[unreadable] increase our understanding of how American ginseng protects from colitis, and possibly other autoimmune[unreadable] conditions and will provide the rationale for expanding into clinical trials.[unreadable]