title: Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice.
abstract: The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great practical and research interest because of its pronounced, widespread physiological effects, primarily antimicrobial and anti-inflammatory, arising from its ability to interact with proteins and DNA. Although CHE was originally shown to possess anti-inflammatory properties, its effects on acute gastric ulcer have not been previously explored. The aim of the present study is to evaluate the protective effect of CHE on ethanol induced gastric ulcer in mice. Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO) activities, macroscopic and histopathological examinations. CHE significantly reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and histological score in a dose-dependent manner. In addition, CHE also significantly inhibited nitric oxide (NO) concentration, pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level in serum and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose-dependent manner. In addition, immunohistochemical analysis revealed that CHE markedly attenuated the overexpression of nuclear factor-κB in gastric mucosa of mice. It was concluded that CHE represents a potential therapeutic option to reduce the risk of gastric ulceration. In addition, acute toxicity study revealed no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest that the gastroprotective activity of CHE might contribute in adjusting the inflammatory cytokine by regulating the NF-κB signalling pathway.
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Li
authors.affiliation: Xi'an Red Cross Hospital, Xi'an 710054, China.
authors.forename: Ding-Jun
authors.initials: DJ
authors.lastname: Hao
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China; Xi'an Red Cross Hospital, Xi'an 710054, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: niuxf@mail.xjtu.edu.cn.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Niu
mesh_terms: D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D053119:Benzophenanthridines; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000431:Ethanol; C016299:chelerythrine; D009195:Peroxidase
keywords: CHE; CMD; Chelerythrine; DAI; ELISA; Ethanol; Gastric ulcer; IL-6; IκB; MAPK; MPO; NF-κB; NO; Nuclear factor-κB; TNF-α; chelerythrine; cimetidine; disease activity index; inhibitor of κB; interleukin-6; mitogen-activated protein kinase; myeloperoxidase; nitric oxide; nuclear factor kappa B; the enzyme immunosorbent assay; tumor necrosis factor-alpha