结肠炎
炎症性肠病
地穴
溃疡性结肠炎
免疫系统
胃肠病学
内科学
医学
免疫学
疾病
作者
Brooke M. Bullard,Sierra J. McDonald,Thomas D. Cardaci,Brandon N. VanderVeen,Ahmed Dawood Mohammed,Jason L. Kubinak,Joseph F. Pierre,Ioulia Chatzistamou,Daping Fan,Lorne J. Hofseth,E. Angela Murphy
出处
期刊:American Journal of Physiology-gastrointestinal and Liver Physiology
[American Physiological Society]
日期:2024-03-12
标识
DOI:10.1152/ajpgi.00004.2024
摘要
Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol - a novel, potent, bioavailable compound found in American ginseng - can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. 14-week-old C57BL/6 female mice were either given 3 rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or 1 round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage 3x/week for the study duration. Consistent with our previous findings, panaxynol significantly (p<0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (p<0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16s sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). Additionally, panaxynol significantly (p<0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.
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