title: Mulberry leaf extract fermented with Lactobacillus acidophilus A4 ameliorates 5-fluorouracil-induced intestinal mucositis in rats.
abstract: 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 10 days and injected intraperitoneally with 5-FU (150 mg kg-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)-1β. 5-FU induced significant weight loss, shortened villi height, and increased histological severity, IL-1β 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-1β expression and MPO level. Interestingly, FME had the greatest protective effect on 5-FU-induced mucositis in rats.
  
  
  CONCLUSIONS
  Our 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-1β 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.
authors.affiliation: R&D Center, Seoul Dairy Cooperative, Ansan, Gyeonggi, South Korea.
authors.forename: N S
authors.initials: NS
authors.lastname: Oh
authors.affiliation: R&D Center, Seoul Dairy Cooperative, Ansan, Gyeonggi, South Korea.|Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors.forename: K W
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Animal Science and Institute of Milk Genomics, Chonbuk National University, Jeonju, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000081:Acetamides / Q000008:administration & dosage; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005285:Fermentation; D005472:Fluorouracil / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000382:microbiology; D007779:Lactobacillus acidophilus / Q000378:metabolism*; D008297:Male; D031625:Morus / Q000382:microbiology*; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage; D018515:Plant Leaves / Q000382:microbiology; D019936:Probiotics / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000081:Acetamides; D016207:Cytokines; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D005472:Fluorouracil
keywords: 5-fluorouracil; intestinal mucositis; mucin; mulberry leaf extract; probiotics