title: Pharmacological mechanisms underlying the anti-ulcer activity of methanol extract and canthin-6-one of Simaba ferruginea A. St-Hil. in animal models.
abstract: CONCLUSIONS
  Simaba ferruginea A. St-Hil. (Simaroubaceae) is a subshrub typical of the Brazilian Cerrado, whose rhizomes are popularly used as infusion or decoction for the treatment of gastric ulcers, diarrhea and fever.
  
  
  OBJECTIVE
  To evaluate the pharmacological mechanism(s) of action of the antiulcer effects of the methanol extract of Simaba ferruginea and its alkaloid canthin-6-one.
  
  
  METHODS
  Rhizome of Simaba ferruginea was macerated with methanol to obtain the methanol extract (MESf) from which was obtained, the chloroform fraction. Canthin-6-one alkaloid (Cant) was purified and then isolated from the chloroform fraction (CFSf). The isolated Cant was identified by HPLC. Anti-ulcer assays were determined using ethanol and indomethacin-induced ulcer models in mice and rats respectively. In order to determine the probable mechanisms of actions of MESf and Cant animals were pretreated with l-NAME prior to anti-ulcer agent treatments and ulcer induction and nitric oxide (NO) level determined in order to assess NO involvement in the gastroprotective effects. Assays of malondialdehyde (MDA), myeloperoxidase (MPO), pro-inflammatory cytokines: interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-α) and prostaglandin E(2) (PGE(2)) were also carried out according to previously described methods.
  
  
  RESULTS
  The results indicate that the antiulcerogenic effects of MESf and Cant in ethanol-induced ulcer is mediated in part through increase in the production of protective endogenous NO as the antiulcerogenic activity of MESf and Cant was reduced in animals pre-treated with l-NAME. In indomethacin-induced ulcer pre-treatment with MESf and Cant showed reduction in the levels of MPO and MDA in the gastric tissue, thus indicating the participation of the antioxidant mechanisms on the gastroprotective effects. The plasma levels of IL-8 in ulcerated rats with indomethacin were also reduced by Cant, but not by MESf, indicating that inhibition of this cytokine contributes to the gastroprotective effect of Cant. However MESf and Cant had no effect on the mucosal membrane levels of PGE(2), indicating that the gastroprotective effects of these agents is independent of PGE(2) modulation.
  
  
  CONCLUSIONS
  The results obtained in this study with MESf and Cant added insights into the pharmacological mechanisms involved in their mode of antiulcer action. The results indicate that Cant is one of the compounds responsible for these effects. Such findings are of extreme importance in the strive for future development of potent, safer and effective antiulcer agent. The efficacy of MESf and Cant in gastroprotection shows that Simaba ferruginea might be a promising antiulcer herbal medicine, in addition to confirming the popular use of this plant against gastric ulcer models utilised in this study.
authors.affiliation: Department of Basic Sciences in Health, Faculty of Medical Sciences, Federal University of Mato Grosso (UFMT), Av. Fernando Correa da Costa, no. 2367, Coxipó, Cuiabá, Mato Grosso Zip Code: 78060-900, Brazil.
authors.forename: Elisângela Saturnino
authors.initials: ES
authors.lastname: de Souza Almeida
authors.forename: Valdir Cechinel
authors.initials: VC
authors.lastname: Filho
authors.forename: Rivaldo
authors.initials: R
authors.lastname: Niero
authors.forename: Bruna Kurz
authors.initials: BK
authors.lastname: Clasen
authors.forename: Sikiru Olaitan
authors.initials: SO
authors.lastname: Balogun
authors.forename: Domingos Tabajara
authors.initials: DT
authors.lastname: de Oliveira Martins
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002243:Carbolines; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D026121:Indole Alkaloids; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D000432:Methanol / Q000737:chemistry; D009287:Naphthyridines / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D029641:Simaroubaceae / Q000737:chemistry*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D002243:Carbolines; D016207:Cytokines; D026121:Indole Alkaloids; D007211:Indoles; D009287:Naphthyridines; D010936:Plant Extracts; C453379:canthin-6-one; D008315:Malondialdehyde; D009195:Peroxidase; D015232:Dinoprostone; D000432:Methanol