Journal
LETTERS IN APPLIED MICROBIOLOGY
Volume 64, Issue 6, Pages 459-468Publisher
WILEY
DOI: 10.1111/lam.12741
Keywords
5-fluorouracil; intestinal mucositis; mucin; mulberry leaf extract; probiotics
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Funding
- High Value-Added Food Technology Development Program of the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (iPET)
- Ministry for Food, Agriculture, Forestry, and Fisheries of Republic of Korea [314068-03-1-HD020]
- National Research Foundation of Korea (NRF
- Seoul, Korea) - Ministry of Science, Information and Communications Technology (ICT) and Future Planning [2016M3C1B5907057]
- National Research Foundation of Korea [2016M3C1B5907057] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The objective of the present study was to evaluate the effect of mulberry leaf extract (ME) fermented with Lactobacillus acidophilus A4 (A4) on intestinal mucositis induced by 5-fluorouracil (5-FU) in a rat model. Male Wistar rats were gavaged with A4, ME, fermented mulberry leaf extract FME) or lafutidine (LAF) for 10days and injected intraperitoneally with 5-FU (150mgkg(-1)) or saline (normal control) on day 7 to induce mucositis. After euthanizing the animals, their small and large intestines were removed for evaluation of histopathologic parameters, myeloperoxidase (MPO) activity, mucin content, and mRNA expression of the mucin gene and pro-inflammatory cytokine interleukin (IL)-1. 5-FU induced significant weight loss, shortened villi height, and increased histological severity, IL-1 expression, and MPO activity compared to the normal control group. These pathological changes were markedly ameliorated by treatment with A4, ME and FME. These treatments also stimulated MUC2 and MUC5AC gene expression and mucin production, and reduced IL-1 expression and MPO level. Interestingly, FME had the greatest protective effect on 5-FU-induced mucositis in rats. Significance and Impact of the StudyOur results suggest that fermented mulberry leaf extract (ME) may provide synergistic therapeutic benefits of both probiotics and natural plant extracts in prevention of 5-fluorouracil-induced mucositis. These impacts are particularly significant given the induction of MUC2 and MUC5AC gene expressions for production of mucins and the reduction of pro-inflammatory cytokine interleukin-1 in gut environments. Therefore, we proposed that enhanced functionality of ME by fermentation of Lactobacillus acidophilus A4 can be applied as food-grade adjuncts for mucositis therapy and prevention in food industry.
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