Gastroprotective effect and mechanism of action of Croton rhamnifolioides essential oil in mice

Cinara Soares Vidal; Anita Oliveira Brito Pereira Bezerra Martins; Andressa de Alencar Silva; Maria Rayane Correia de Oliveira; Jaime Ribeiro-Filho; Thaís Rodrigues de Albuquerque; Henrique Douglas Melo Coutinho; Jackson Roberto Guedes da Silva Almeida; Lucindo Jose Quintans Junior; Irwin Rose Alencar de Menezes

doi:10.1016/j.biopha.2017.02.005

Gastroprotective effect and mechanism of action of Croton rhamnifolioides essential oil in mice

Biomed Pharmacother. 2017 May:89:47-55. doi: 10.1016/j.biopha.2017.02.005. Epub 2017 Feb 17.

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ 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.

PMID: 28214687
DOI: 10.1016/j.biopha.2017.02.005

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.

Hypothesis/purpose: 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.

Conclusion: 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.

Keywords: Chemical profile; Croton rhamnifolioides; Essential oil; Gastroprotection; Mechanism of action.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal
Anti-Ulcer Agents / pharmacology*
Croton / chemistry
Croton Oil / pharmacology*
Croton Oil / toxicity
Ethanol
Female
Gastric Mucosa / drug effects
Indomethacin
Lethal Dose 50
Male
Mice
Plant Leaves / chemistry
Protective Agents / pharmacology*
Signal Transduction / drug effects
Stomach Diseases / prevention & control*
Stomach Ulcer / chemically induced
Stomach Ulcer / prevention & control

Substances

Anti-Inflammatory Agents, Non-Steroidal
Anti-Ulcer Agents
Protective Agents
Ethanol
Croton Oil
Indomethacin