Therapeutic actions of methyl eugenol in acute lung inflammation induced in rats

• Published in: South African journal of botany Vol. 169; pp. 341 - 349
• Main Authors: de Sousa, Maria Alana Rocha, Teixeira, Guilherme dos Santos, Marquesa, Rosemarie Brandim, de Sousa, Luciana Mendes Ribeiro, Ramos, Ricardo Martins, Bento, Ricardo Rodrigues de França, Neto, Bartolomeu Cruz Viana, Gusmão, Suziete Batista Soares, Sá, José Luiz Silva, Filho, Antônio Luiz Martins Maia, Lobo, Anderson Oliveira, Gusmão, Gustavo Oliveira de Meira
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.06.2024
• Subjects: Ischemia-reperfusion injury; Methyl eugenol; Molecular docking; Therapeutic approach; Ischemia-reperfusion injury; Therapeutic approach; Methyl eugenol; Molecular docking
• ISSN: 0254-6299; 1727-9321
• DOI: 10.1016/j.sajb.2024.04.023

•Computer simulations and the Lipinski rule evaluate the pharmacokinetic and toxicological aspects of methyl eugenol as a drug candidate.•Treatment with methyl eugenol (ME) during and after the initiation of acute respiratory distress syndrome (ARDS) can prevent the progression of acute inflammation.•In vivo and in silico tests indicate that ME oil is an orally bioavailable drug that exerts multifunctional cytoprotective activities.•ME oil can treat and prevent intestinal I/R-induced ARDS in rats. Acute respiratory distress syndrome (ARDS) is an inflammatory disease that affects the lungs with rupture of the alveolar-capillary barrier and loss of lung compliance, orchestrated by an intense inflammatory process mediated by neutrophils that culminates in diffuse alveolar data and tissue hypoxia. In this context, no specific drug has yet been applied to treat the syndrome. Therefore, finding new therapeutic targets that can treat the syndrome has become a research study. In view of this, methyl-eugenol (ME) has become the target of this study. The aim of this work was to carry out an in silico pharmacological and toxicological analysis with ADMET, as well as to determine, by means of molecular docking, the interaction affinity of the 5-LOX and COX-2 enzymes with ME and then the in vivo tests; in which male rats were distributed into five groups with five rats each, in which some groups were subjected to the process of ischemia and reperfusion (I/R). Groups G4 and G5 were treated by inhalation with ME (10 %). After completing these procedures, statistical analysis and lung histology were carried out. In the ADMET prediction, ME showed high intestinal absorption and a medium-permeability blood-brain barrier. ME had no violations of Lipinski's rule, demonstrating high potential as a drug candidate. Molecular docking showed that ME had the highest binding affinity with the 5-LOX enzyme. Finally, the statistical and histological analyses of the in vivo test showed acute and accentuated lung damage in the G1 group, while in the G4 and G5 groups, ME showed pharmacological efficacy, reducing the number of inflammatory cells, free macrophages and free radicals. The results indicate that ME oil is a favorable therapeutic approach in the treatment of ARDS.