title: Gastroprotective effect and mechanism of action of Croton rhamnifolioides essential oil in mice.
abstract: BACKGROUND
  Croton rhamnifolioides Pax is a plant species that have been used in the folk medicine to treat ulcers, inflammations and hypertension. However, despite the relevant data obtained from ethnopharmacological studies, the pharmacological properties endorsing the efficacy of this plant to treat ulcer remain to be elucidated.
  
  
  OBJECTIVE
  The present study aimed to characterize the chemical profile and evaluate the gastroprotective activity of the essential oil obtained from C. rhamnifolioides Pax (OECC) in mice.
  
  
  METHODS
  The essential oil of Croton rhamnifolioides was obtained by hydrodistillation and analyzed by gas-phase chromatography coupled to mass spectrometry (GC/MS). The median lethal dose was determined employing an acute toxicity test. The gastroprotective activity of the OECC was investigated using animal models of gastric ulcer induced by the administration of absolute ethanol, acidified ethanol or indomethacin. Mechanisms of action were investigated using the physical barrier test and by in vivo evaluation of the involvement of the following molecular pathways: nitric oxide, ATP - dependent potassium channels, α2- noradrenergic receptors, capsaicin - sensitive afferent neurons and opioid receptor.
  
  
  RESULTS
  We identified the presence of 21 compounds in OECC, including spathulenol and 1,8 - cineole as major constituents. In orally administered mice, OECC caused no significant toxicity. OECC significantly prevented gastric lesions in all mice models. The barrier test demonstrated that the gastroprotective activity of OECC occurs in a systemic dimension. Our results demonstrated that the gastroprotective effect of OECC involves mechanisms that are related to modulation of opioid receptors and nitric oxide.
  
  
  CONCLUSIONS
  In conclusion, OECC demonstrated significant gastroprotective activity associated with low toxicity, providing scientific evidences that C. rhamnifolioides have the potential for the development of new antiulcer drugs.
authors.affiliation: Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, 63105-000, Crato, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: cinaravidal@hotmail.com.
authors.forename: Cinara Soares
authors.initials: CS
authors.lastname: Vidal
authors.affiliation: Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, 63105-000, Crato, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: anitaoliveirab4@yahoo.com.br.
authors.forename: Anita
authors.initials: A
authors.lastname: Oliveira Brito Pereira Bezerra Martins
authors.affiliation: Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, 63105-000, Crato, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: andressaalencara7@hotmail.com.
authors.forename: Andressa
authors.initials: A
authors.lastname: de Alencar Silva
authors.affiliation: Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, 63105-000, Crato, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: rayane_braya@hotmail.com.
authors.forename: Maria Rayane Correia
authors.initials: MRC
authors.lastname: de Oliveira
authors.affiliation: Leao Sampaio University Center, Juazeiro do Norte, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: jaimeribeirofilho@gmail.com.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ribeiro-Filho
authors.affiliation: Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, 63105-000, Crato, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: thaysrodrigues_albuquerque@hotmail.com.
authors.forename: Thaís Rodrigues
authors.initials: TR
authors.lastname: de Albuquerque
authors.affiliation: Laboratory of Microbiology and Biology Molecular, Department of Biological Chemistry, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, 63105-000, Crato, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: hdmcoutinho@gmail.com.
authors.forename: Henrique Douglas Melo
authors.initials: HDM
authors.lastname: Coutinho
authors.affiliation: Department of Pharmacy, Federal University of Vale do São Francisco, 56.304-205, Petrolina, PE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: jackson.guedes@univasf.edu.br.
authors.forename: Jackson Roberto Guedes
authors.initials: JRG
authors.lastname: da Silva Almeida
authors.affiliation: Department of Pharmacy, Federal University of Vale do São Francisco, 56.304-205, Petrolina, PE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: lucindojr@gmail.com.
authors.forename: Lucindo Jose
authors.initials: LJ
authors.lastname: Quintans
authors.affiliation: Laboratory of Pharmacology and Molecular Chemistry, Department of Biological Chemistry, Regional University of Cariri, Cel Antonio Luis 1161, Pimenta, 63105-000, Crato, CE, Brazil; Department of Physiology, Federal University of Sergipe, São Cristóvão, 49100-000, Aracaju, SE, Brazil. Electronic address: irwin.alencar@urca.br.
authors.forename: Irwin Rose Alencar
authors.initials: IRA
authors.lastname: de Menezes
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D029802:Croton / Q000737:chemistry; D003436:Croton Oil / Q000494:pharmacology* / Q000633:toxicity; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D007213:Indomethacin; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D018515:Plant Leaves / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013272:Stomach Diseases / Q000517:prevention & control*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D020011:Protective Agents; D000431:Ethanol; D003436:Croton Oil; D007213:Indomethacin
keywords: Chemical profile; Croton rhamnifolioides; Essential oil; Gastroprotection; Mechanism of action