title: Protective effect and potential mechanisms of Wei-Chang-An pill on high-dose 5-fluorouracil-induced intestinal mucositis in mice.
abstract: BACKGROUND
  Wei-Chang-An pill (WCA pill), a traditional Chinese pharmaceutical preparation, possessed potential anti-inflammatory advantages and noteworthy gastrointestinal regulations in digestive diseases, which might represent a promising candidate for the treatment of intestinal mucositis (IM) induced by 5-fluorouracil (5-FU).
  
  
  OBJECTIVE
  To analyze the bioactive constituents and investigate the effect of methanol extraction from WCA pill (WCA ext) on 5-FU induced IM with underlying mechanisms.
  
  
  METHODS
  The analysis of serum bioactive constituents after WCA ext administration in rats was carried out by UHPLC-Quadrupole-Time of Flight-Mass Spectrometry. In mice, IM was induced by 5-FU and physical manifestations were measured during the period of drug delivery. Half of mice were assessed with histology, expression of inflammatory cytokines in ileum and plasma via hematoxylin and eosin staining, immunohistochemical staining as well as cytokine enzyme-linked immunosorbent assay test, respectively. Besides, gastric emptying (GE) and gastrointestinal transit (GIT) were further tested in the other half of 5-FU induced mice.
  
  
  RESULTS
  Twenty-two compounds were identified or tentatively characterized. IM induced by 5-FU was improved significantly after treatment with WCA ext through reducing the body weight loss, relieving the severe diarrhea, and inhibiting the GE as well as GIT. Further assessments validated that WCA ext promoted the recovery of intestinal mucosa, evaluated the activity of enterocyte proliferation, maintained the integrity of tight junction, and ameliorated the inflammatory disturbances.
  
  
  CONCLUSIONS
  These results suggested that WCA ext promoted the restoration of intestinal function in 5-FU-induced IM via regulating multiple sites of actions in intestinal homeostasis. Accordingly, WCA pill might be a promising therapeutic candidate for the prevention of IM during cancer chemotherapy.
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pharmacy, Logistics University of Chinese People's Armed Police Forces, Special Drugs R & D Center of People's Armed Police Forces, Tianjin 300162, China. Electronic address: zhangjingze1977@163.com.
authors.forename: Jingze
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Tianjin Lerentang Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co., Ltd., Tianjin 300380, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tianjin Lerentang Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co., Ltd., Tianjin 300380, China.
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: pharmgao@tju.edu.cn.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000097:blood; D019610:Cytoprotection; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005472:Fluorouracil / Q000633:toxicity*; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D013058:Mass Spectrometry; D000432:Methanol / Q000737:chemistry; D051379:Mice; D052016:Mucositis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D017208:Rats, Wistar; D012997:Solvents / Q000737:chemistry; D013607:Tablets; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D012997:Solvents; D013607:Tablets; C545640:Wei-Chang-An-Wan; D005472:Fluorouracil; D000432:Methanol
keywords: 5-Fluorouracil; Chemotherapy; Diarrhea; Intestinal mucositis; Wei-Chang-An pill