Chaparala Anusha, Poudyal Deepak, Tashkandi Hossam, Witalison Erin E, Chumanevich Alexander A, Hofseth Jenna L, Nguyen Ivy, Hardy Olivia, Pittman Douglas L, Wyatt Michael D, Windust Anthony, Murphy Elizabeth A, Nagarkatti Mitzi, Nagarkatti Prakash, Hofseth Lorne J
Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA.
Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Oncotarget. 2020 Jun 2;11(22):2026-2036. doi: 10.18632/oncotarget.27592.
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.
溃疡性结肠炎对患者的生活质量有重大影响,并且会大幅增加长期患病患者患结肠癌的风险。传统治疗只能提供有限的缓解,且副作用风险高,而补充和替代药物可以提供安全有效的选择。在过去十年中,我们已经表明西洋参及其己烷馏分(HAG)具有抗氧化和抗炎特性,可抑制小鼠结肠炎并预防结肠炎相关的结肠癌。为了分离出单一活性化合物,我们进一步对HAG进行了分馏,发现该馏分中最丰富的分子是聚乙炔人参炔醇(PA)。在分离和鉴定PA之后,我们测试了PA在治疗和预防小鼠结肠炎方面的功效,并研究了其作用机制。我们在此证明,PA通过靶向巨噬细胞导致DNA损伤和凋亡,有效治疗葡聚糖硫酸钠小鼠模型中的结肠炎。这项研究提供了更多的机制证据,表明西洋参可用于结肠炎及其他与巨噬细胞功能障碍相关疾病的常规治疗。