title: Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway.
abstract: Evodiamine (EVD), a major alkaloid compound extracted from the dry unripened fruit Evodia fructus (Evodia rutaecarpa Benth., Rutaceae), has various pharmacological effects. The purpose of the present study was to investigate the possible anti-ulcerogenic potential of EVD and explore the underlying mechanism against ethanol-induced gastric ulcer in mice. Administration of EVD at the doses of 20, 40mg/kg body weight prior to the ethanol ingestion could effectively protect the stomach from ulceration. The gastric lesion was significantly ameliorated in the EVD group compared with that in the model group. Pre-treatment with EVD prevented the oxidative damage and decreased the levels of prostaglandin E2 (PGE2) content, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, EVD pretreatment markedly increased the serum levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), decreased malonaldehyde (MDA) content in serum and activity of myeloperoxidase (MPO) in stomach tissues compared with those in the model group. In the mechanistic study, significant elevation of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 expressions were observed in the gastric mucosa group, whereas EVD effectively suppressed the protein expressions of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 in mice. Moreover, EVD showed protective activity on ethanol-induced GES-1 cells, while the therapeutic effects were not due to its cytotoxity. Taken together, these results strongly indicated that EVD exerted a gastro-protective effect against gastric ulceration. The underlying mechanism might be associated with the improvement of antioxidant and anti-inflammatory status through Rho/NF-κB pathway.
authors.affiliation: The Third Teaching Hospital, Jilin University, Changchun 130033, China.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Shilin
authors.initials: S
authors.lastname: Gong
authors.affiliation: The Third Teaching Hospital, Jilin University, Changchun 130033, China; Changchun University of Chinese Medicine, Changchun 130117, China. Electronic address: wangshuminch@126.com.
authors.forename: Shumin
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Third Teaching Hospital, Jilin University, Changchun 130033, China; Changchun University of Chinese Medicine, Changchun 130117, China. Electronic address: machunhuabest@126.com.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ma
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000097:blood; D002460:Cell Line; D015232:Dinoprostone / Q000097:blood; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008315:Malondialdehyde / Q000097:blood; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D015850:Interleukin-6; D016328:NF-kappa B; D011799:Quinazolines; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D000431:Ethanol; D008315:Malondialdehyde; C049639:evodiamine; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D015232:Dinoprostone
keywords: Ethanol; Evodiamine; Gastric ulcer; Rho