Anti-inflammatory mechanisms of American ginseng in colitis

溃疡性结肠炎(UC)是一种免疫调节的慢性炎症性疾病。大约4 全球有数百万人患有结肠癌，并面临更高的结肠癌风险。常规治疗 治疗结肠炎可以缩短疾病活动期并有助于保持缓解，但这些治疗方法通常 与副作用相关，并有边际结果。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甲基维他命治疗或草药/膳食补充剂。那里 然而，没有关于UC患者服用西洋参来缓解症状和体征的文献 结肠炎。在目前的研究中，我们提出了令人兴奋的数据，人参抑制了两只小鼠结肠炎的发生 结肠炎模型以及预防结肠炎引起的结肠癌。这笔赠款旨在了解 这种抑制的机制是未来人类临床试验的必要前提。我们将测试 饮食补充西洋参可抑制大鼠UC相关炎症 结肠通过诱导免疫细胞凋亡，改变Th1/Th2细胞因子的机制 免疫细胞迁移和贩运的概况和/或变化。因为人参还能抑制结肠炎-- 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 和结肠细胞中的蛋白质硝化。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一种途径抑制pRb的过度磷酸化 特定的激酶通路的激活减少。我们将调查人参是否调节这些 通过对结肠细胞和/或免疫细胞的直接作用产生影响。最后，我们建议划定 西洋参的有效成分对结肠炎有抑制作用。总而言之，这项研究将 增加我们对西洋参如何预防结肠炎和可能的其他自身免疫的理解 并将为扩大到临床试验提供理论基础。

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.