Panaxynol, a bioactive component of American ginseng, targets macrophages and suppresses colitis in mice

Abstract

// Anusha Chaparala 1 , Deepak Poudyal 2 , Hossam Tashkandi 1 , Erin E. Witalison 3 , Alexander A. Chumanevich 1 , Jenna L. Hofseth 1 , Ivy Nguyen 1 , Olivia Hardy 1 , Douglas L. Pittman 1 , Michael D. Wyatt 1 , Anthony Windust 4 , Elizabeth A. Murphy 5 , Mitzi Nagarkatti 5 , Prakash Nagarkatti 5 and Lorne J. Hofseth 1 1 Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA 2 Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA 3 Department of Biological and Biomedical Sciences, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Kannapolis, NC, USA 4 Measurement Science and Standards, National Research Council, Ottawa, ON, Canada 5 Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA Correspondence to: Lorne J. Hofseth, email: [email protected] Keywords: inflammatory bowel diseases; ulcerative colitis; American ginseng; panaxynol; macrophages Received: January 19, 2020     Accepted: April 03, 2020     Published: June 02, 2020 ABSTRACT 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 both American ginseng and its hexane fraction (HAG) have 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 HAG, and found the most abundant molecule in this fraction was the polyacetylene, panaxynol (PA). After isolating and characterizing PA, we tested the efficacy of PA in the treatment and prevention of colitis in mice and studied the mechanism of action. We demonstrate here that PA effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. This study provides additional mechanistic evidence that American ginseng can be used for conventional treatment of colitis and other diseases associated with macrophage dysfunction.

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