Department of OB/GYN, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Nutrients. 2020 Jun 21;12(6):1850. doi: 10.3390/nu12061850.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects millions of people worldwide and increases the risk of colorectal cancer (CRC) development. We have previously shown that American ginseng (AG) can treat colitis and prevent colon cancer in mice. We further fractionated AG and identified the most potent fraction, hexane fraction (HAG), and the most potent compound in this fraction, panaxynol (PA). Because (1) oxidative stress plays a significant role in the pathogenesis of colitis and associated CRC and (2) nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses, we examined the role of Nrf2 as a mechanism by which AG suppresses colitis. Through a series of in vitro and in vivo Nrf2 knockout mouse experiments, we found that AG and its components activate the Nrf2 pathway and decrease the oxidative stress in macrophages (mΦ) and colon epithelial cells in vitro. Consistent with these in vitro results, the Nrf2 pathway is activated by AG and its components in vivo, and Nrf2 mice are resistant to the suppressive effects of AG, HAG and PA on colitis. Results from this study establish Nrf2 as a mediator of AG and its components in the treatment of colitis.
溃疡性结肠炎（UC）是一种慢性炎症性肠病，影响着全球数百万人，并增加结直肠癌（CRC）发展的风险。我们之前已经表明，西洋参（AG）可以治疗结肠炎并预防小鼠结肠癌。我们进一步对 AG 进行了分离，并确定了最有效的部分，己烷部分（HAG），以及该部分中最有效的化合物，人参炔醇（PA）。由于（1）氧化应激在结肠炎和相关 CRC 的发病机制中起重要作用，（2）核因子红细胞 2 相关因子 2（Nrf2）是抗氧化反应的主要调节剂，我们研究了 Nrf2 作为 AG 抑制结肠炎的机制。通过一系列体外和体内 Nrf2 敲除小鼠实验，我们发现 AG 及其成分在体外激活 Nrf2 途径并降低巨噬细胞（mΦ）和结肠上皮细胞中的氧化应激。与这些体外结果一致，AG 及其成分在体内激活 Nrf2 途径，并且 Nrf2 小鼠对 AG、HAG 和 PA 抑制结肠炎的作用具有抗性。这项研究的结果确立了 Nrf2 作为 AG 及其成分治疗结肠炎的介质。
