Anti-inflammatory mechanisms of American ginseng in colitis

溃疡性结肠炎（UC）是一种免疫介导的慢性炎症性疾病。约4 全世界有1000万人患有这种疾病，并且结肠癌的风险增加。常规治疗 结肠炎的治疗可以减少疾病的活动期，并有助于维持缓解，但这些治疗往往 与副作用相关，并且具有边际结果。出于这个原因，许多结肠炎患者转向 补充和替代治疗，希望减轻活动性疾病的症状。据估计 大约50%的UC患者使用某种形式的巨维生素治疗或草药/膳食补充剂。那里 然而，没有关于UC患者服用西洋参来缓解体征和症状的文献 结肠炎在目前的研究中，我们提出了令人兴奋的数据，人参抑制结肠炎的发病在两个小鼠 结肠炎模型以及预防结肠炎导致的结肠癌。该基金旨在了解 这种抑制机制作为未来人体临床试验的必要先决条件。我们将测试 西洋参膳食补充剂抑制UC相关炎症的假设 结肠通过机制，涉及诱导免疫细胞凋亡，改变Th 1/Th 2细胞因子 谱和/或免疫细胞迁移和运输的变化。因为人参也能抑制结肠炎- 癌症序列在我们的模型中，我们将检查它是否抑制炎症驱动的DMA损伤 和蛋白质硝化。由于pRb在结肠炎中过度磷酸化和失活，我们将 进一步研究人参是否通过涉及以下机制抑制pRb过度磷酸化： 减少特定激酶途径的激活。我们将研究人参是否介导这些 通过直接作用于结肠细胞和/或免疫细胞而产生作用。最后，我们建议划定 活性成分的西洋参负责抑制结肠炎。这项研究将 增加我们对西洋参如何预防结肠炎和其他自身免疫性疾病的了解， 条件，并将提供扩展到临床试验的理由。

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