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

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.