Molecules from American Ginseng Suppress Colitis through Nuclear Factor Erythroid-2-Related Factor 2

• Published in: Nutrients 2020-06, Vol.12 (6), p.1850
• Main Authors: Chaparala, Anusha, Tashkandi, Hossam, Chumanevich, Alexander A, Witalison, Erin E, Windust, Anthony, Cui, Taixing, Nagarkatti, Mitzi, Nagarkatti, Prakash, Hofseth, Lorne J
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Cancer; Cell culture; Colitis; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colon; Colon cancer; Colorectal carcinoma; Diynes - pharmacology; Diynes - therapeutic use; Epithelial cells; Fatty Alcohols - pharmacology; Fatty Alcohols - therapeutic use; Ginseng; HCT116 Cells; Health risks; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Macrophages; mice; Mice, Inbred C57BL; Mice, Knockout; NF-E2-Related Factor 2 - metabolism; NFE2L2; Nrf2; Oxidative stress; Oxidative Stress - drug effects; Panax - chemistry; panaxynol; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Transcription factors; ulcerative; Ulcerative colitis
• ISSN: 2072-6643; 2072-6643
• 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.