Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways

Author(s):Show less -

Santana, Fernanda P. R. ^{[1, 2]} ; da Silva, Rafael C. ^[1] ; Ponci, Vitor ^[1] ; Pinheiro, Aruana J. M. C. R. ^{[3, 4]} ; Olivo, Clarice R. ^[2] ; Caperuto, Luciana C. ^[1] ; Arantes-Costa, Fernanda M. ^[2] ; Claudio, Samuel R. ^[5] ; Ribeiro, Daniel A. ^[5] ; Tiberio, Iolanda F. L. C. ^[2] ; Lima-Neto, Lidio G. ^{[3, 4]} ; Lago, Joao Henrique G. ^[6] ; Prado, Carla M. ^[5]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biol Sci, Diadema, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Med, Sao Paulo, SP - Brazil

^[3] Univ CEUMA, Sao Luis, MA - Brazil

^[4] Programa Posgrad Rede BIONORTE, Sao Luis, Maranhao - Brazil

^[5] Univ Fed Sao Paulo, Dept Biosci, Rua Silva Jardim 136, BR-11015020 Santos, SP - Brazil

^[6] Fed Univ ABC, Ctr Nat Sci & Humanities, Santo Andre, SP - Brazil

• Document type: Journal article
• Source: Biochemical Pharmacology; v. 180, OCT 2020.
• Web of Science Citations: 2

Abstract

Background: Eugenol, a common phenylpropanoid derivative found in different plant species, has well-described anti-inflammatory effects associated with the development of occupational hypersensitive asthma. Dehydrodieugenol, a dimeric eugenol derivative, exhibits anti-inflammatory and antioxidant activities and can be found in the Brazilian plant species Nectandra leucantha (Lauraceae). The biological effects of dehydrodieugenol on lung inflammation remain unclear. Purpose: This study aimed to investigate the effects of eugenol and dehydrodieugenol isolated from N. leucantha in an experimental model of asthma. Methods: In the present work, the toxic effects of eugenol and dehydrodieugenol on RAW 264.7 cells and their oxidant and inflammatory effects before lipopolysaccharide (LPS) exposure were tested. Then, male BALB/c mice were sensitized with ovalbumin through a 29-day protocol and treated with vehicle, eugenol, dehydrodieugenol or dexamethasone for eight days beginning on the 22nd day until the end of the protocol. Lung function; the inflammatory profile; and the protein expression of ERK1/2, JNK, p38, VAChT, STAT3, and SOCS3 in the lung were evaluated by immunoblotting. Results: Eugenol and dehydrodieugenol were nontoxic to cells. Both compounds inhibited NO release and the gene expression of IL-1 beta and IL-6 in LPS-stimulated RAW 264.7 cells. In OVA-sensitized animals, dehydrodieugenol reduced lung inflammatory cell numbers and the lung concentrations of IL-4, IL-13, IL-17, and IL-10. These anti-inflammatory effects were associated with inhibition of the JNK, p38 and ERK1/2, VAChT and STAT3/SOCS3 pathways. Moreover, treatment with dehydrodieugenol effectively attenuated airway hyperresponsiveness. Conclusion: The obtained data demonstrate, for the first time, that dehydrodieugenol was more effective than eugenol in counteracting allergic airway inflammation in mice, especially its inhibition of the JNK, p38 and ERK1/2, components of MAPK pathway. Therefore, dehydrodieugenol can be considered a prototype for the development of new and effective agents for the treatment of asthmatic patients. (AU)

• FAPESP's process: 14/25689-4 - Effects of cholinergic system in acute and chronic pulmonary inflammation
• Grantee: Carla Máximo Prado
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/06088-0 - Effects of eugenol and dehidrodieugenol isolated from Nectandra leucantha (Lauraceae) treatments in experimental models of acute and chronic lung disease
• Grantee: Carla Máximo Prado
• Support Opportunities: Regular Research Grants