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.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Anastasiya A. Chumanevich1, Anusha Chaparala1, Erin E. Witalison1, Hossam Tashkandi1, Anne B. Hofseth1, Corey Lane1, Edsel Pena2, Piaomu Liu2, Doug L. Pittman1, Prakash Nagarkatti3, Mitzi Nagarkatti3, Lorne J. Hofseth1 and Alexander A. Chumanevich1 1 Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, SC, USA 2 Department of Statistics, University of South Carolina, Columbia, SC, USA 3 School of Medicine, University of South Carolina, Columbia, SC, USA Correspondence to: Alexander A. Chumanevich, email: // <![CDATA[ mail("chumanev","mailbox.sc",14,"") // ]]> Keywords: colitis, colon, inflammation, dextran sulfate sodium, CAM, FDA Received: November 11, 2016 Accepted: November 15, 2016 Published: December 10, 2016

Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that American ginseng has anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis associated colon cancer. With the goal of isolating a single active compound, we further fractionated the hexane fraction, and found the most abundant molecule in this fraction was the polyacetylene, Panaxynol. After isolating and characterizing Panaxynol, we tested the efficacy of Panaxynol in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that Panaxynol effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. Positive outcomes from this study could take American ginseng one-step further towards becoming a conventional drug for the treatment of colitis, and possibility exploring other autoimmune diseases associated with macrophage dysfunction.