title: Mechanisms of action underlying the gastric antiulcer activity of the Rhizophora mangle L.
abstract: BACKGROUND
  Rhizophora mangle, the red mangrove, has long been known as a traditional antiulcer medicine. The present work evaluated the mechanisms of action involved in the anti-ulcer properties of the Rhizophora mangle bark extracts.
  
  
  METHODS
  Gastroprotection of Rhizophora mangle was evaluated in rodent experimental models (ethanol). To elucidate the mechanisms of action the antisecretory action and involvement of NO, SH, mucus and PGE(2) were evaluated. The acetic acid-induced gastric ulcer model, Western blotting assay (COX-1, COX-2 and EGF) and immunohistochemical localization of HSP-70, PCNA and COX-2 were also used to evaluate the Rhizophora mangle healing properties.
  
  
  RESULTS
  Results showed that Rhizophora mangle bark crude extract (CE), as well as ethyl acetate (EtOAc) and butanolic fractions (BuOH) provided significant gastroprotection at all the tested doses. Thereby, the following protocols were performed using the lowest dose capable of producing the most effective gastroprotection, which was the BuOH 0.5mg/kg (P<0.001). Several mechanisms are involved in the antiulcer activity of Rhizophora mangle, such as, participation of NO, SH and mucus. The enhancement of PGE(2) levels and the upregulation of COX-2 and EGF seem to be directly linked to the antisecretory, cytoprotective and healing effects of BuOH. HSP-70 and PCNA are also involved in this cicatrisation process. No sign of toxicity was observed in this study, considering the analyzed parameters.
  
  
  CONCLUSIONS
  Our study reinforces its traditional medicinal use. Considering that the current therapies are based on the use of antisecretory or cytoprotective drugs, the Rhizophora mangle arises as a promising alternative antiulcer therapy.
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, UNICAMP, Campinas, SP, Brazil. defaria.felipe@yahoo.com.br
authors.forename: Felipe Meira
authors.initials: FM
authors.lastname: de-Faria
authors.forename: Ana Cristina Alves
authors.initials: AC
authors.lastname: Almeida
authors.forename: Anderson
authors.initials: A
authors.lastname: Luiz-Ferreira
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Dunder
authors.forename: Christiane
authors.initials: C
authors.lastname: Takayama
authors.forename: Maria Silene
authors.initials: MS
authors.lastname: da Silva
authors.forename: Marcelo Aparecido
authors.initials: MA
authors.lastname: da Silva
authors.forename: Wagner
authors.initials: W
authors.lastname: Vilegas
authors.forename: Ariane Leite
authors.initials: AL
authors.lastname: Rozza
authors.forename: Cláudia Helena
authors.initials: CH
authors.lastname: Pellizzon
authors.forename: Walber
authors.initials: W
authors.lastname: Toma
authors.forename: Alba Regina Monteiro
authors.initials: AR
authors.lastname: Souza-Brito
mesh_terms: D019342:Acetic Acid; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D000431:Ethanol; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008519:Medicine, Traditional; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043982:Rhizophoraceae; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D008565:Membrane Proteins; D010936:Plant Extracts; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D000431:Ethanol; D004815:Epidermal Growth Factor; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; D019342:Acetic Acid; D019331:NG-Nitroarginine Methyl Ester