Intestinal inflammation caused by anti-cancer drugs is ameliorated by ginsenoside

IF 10.3 2区 医学 Q1 PHYSIOLOGY
Taisei Tsujii, D. Kato, S. Jonan, K. Amagase
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引用次数: 0

Abstract

Background & Aim: It has been reported that 5-fluorouracil (5-FU), a widely used anticancer drug, causes intestinal inflammation due to shortening of small intestinal villi and destruction of the glandular fossa, resulting in diarrhea and weight loss. Although Ginsenoside Rd (GRd) and Ginsenoside Re (GRe) are saponins found in carrots and have been reported to have anti-inflammatory effects on the gastrointestinal tract, these compounds have not been reported to have anti-inflammatory effects on the small intestinal mucositis induced by 5-FU. In the present study, we investigated the effects of GRd and GRe on the 5-FU-induced mucoenteritis. Materials & Methods: Male C57BL/6N mice (20-25 g) were treated with 5-FU (50 mg/kg i.p.) and GRd (60 or 100 mg/kg p.o.) or GRe (100 mg/kg p.o.) once daily for 7~8 days. 5-FU was dissolved in saline and GRd and GRe were dissolved in 0.5 % CMC. The group receiving saline and 0.5% CMC was designated as the Vehicle group. Body weight and degree of diarrhea (score 0: normal stools, 1: soft stools, 2: severe soft stools, 3: diarrhea, 4: severe diarrhea) were measured daily during the treatment period. The degree of intestinal inflammation was evaluated by histopathological examination using hematoxylin/eosin (H&E) staining, measurement of myeloperoxidase (MPO) activity, and mRNA expression of inflammation-related molecules after the end of drug administration. The expression of NF-κB in the small intestine was examined by immunohistochemical staining. Results: Decreased body weight and exacerbation of diarrhea were observed from the third day of 5-FU administration, and combined administration of GRd or GRe had no effect on these symptoms. Histopathological observations showed that 5-FU administration shortened small intestinal villi and reduced the number of small intestinal crypt, compared to the vehicle group. However, co-administration of GRd and GRe, significantly suppressed the decrease in the number of small intestinal crypts and cells in the crypt by 5-FU treatment and tended to suppress the increase in expression of TNF-α mRNA. MPO activity in the small intestinal mucosa were increased by 5-FU treatment, and the increase was clearly suppressed in the GRd or GRe combination treatment groups. In addition, the expression of NF-κB was clearly increased at 24 hours after the last dose of 5-FU compared with the Vehicle group, and the increase of NF-κB expression by 5-FU administration was clearly suppressed by the concomitant use of GRd. Conclusion: The results obtained in this study suggest that GRd and GRe show anti-inflammatory effect against 5-FU-induced enteritis and that NF-κB is involved in their action. The authors declare no conflict of interest. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
人参皂苷可改善抗癌药物引起的肠道炎症
背景与目的:据报道,5-氟尿嘧啶(5-FU)是一种广泛应用的抗癌药物,由于小肠绒毛缩短和腺窝破坏而引起肠道炎症,导致腹泻和体重减轻。虽然人参皂苷Rd (GRd)和人参皂苷Re (GRe)是在胡萝卜中发现的皂苷,并且有报道对胃肠道有抗炎作用,但这些化合物对5-FU诱导的小肠黏膜炎没有报道。在本研究中,我们研究了GRd和GRe对5- fu诱导的粘膜肠炎的影响。材料与方法:雄性C57BL/6N小鼠(20 ~ 25 g),每日1次,5-FU (50 mg/kg每日)加GRd(60或100 mg/kg每日)或GRe (100 mg/kg每日),连续7~8 d。5-FU溶解于生理盐水中,GRd和GRe溶解于0.5% CMC中。以生理盐水加0.5% CMC组为Vehicle组。在治疗期间每天测量体重和腹泻程度(0分:正常便,1分:软便,2分:严重软便,3分:腹泻,4分:严重腹泻)。通过苏木精/伊红(H&E)染色的组织病理学检查、髓过氧化物酶(MPO)活性测定和给药结束后炎症相关分子mRNA表达来评估肠道炎症程度。免疫组化染色检测小肠组织中NF-κB的表达。结果:5-FU给药第3天体重下降,腹泻加重,GRd或GRe联合给药对上述症状无影响。组织病理学观察显示,与载药组相比,5-FU给药组小肠绒毛缩短,小肠隐窝数量减少。然而,GRd和GRe联合给药可显著抑制5-FU治疗小肠隐窝和隐窝细胞数量的减少,并有抑制TNF-α mRNA表达增加的趋势。5-FU处理小肠黏膜MPO活性升高,GRd或GRe联合处理组明显抑制MPO活性升高。此外,末次给药后24小时NF-κB的表达较Vehicle组明显升高,同时联合使用GRd明显抑制5-FU对NF-κB表达的升高。结论:本研究结果提示GRd和GRe对5- fu诱导的肠炎具有抗炎作用,其作用机制可能与NF-κB有关。作者声明无利益冲突。这是在2023年美国生理学峰会上发表的完整摘要,仅以HTML格式提供。此摘要没有附加版本或附加内容。生理学没有参与同行评议过程。
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来源期刊
Physiology
Physiology 医学-生理学
CiteScore
14.50
自引率
0.00%
发文量
37
期刊介绍: Physiology journal features meticulously crafted review articles penned by esteemed leaders in their respective fields. These articles undergo rigorous peer review and showcase the forefront of cutting-edge advances across various domains of physiology. Our Editorial Board, comprised of distinguished leaders in the broad spectrum of physiology, convenes annually to deliberate and recommend pioneering topics for review articles, as well as select the most suitable scientists to author these articles. Join us in exploring the forefront of physiological research and innovation.
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