Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways
Carregando...
Citações na Scopus
20
Tipo de produção
article
Data de publicação
2020
Título da Revista
ISSN da Revista
Título do Volume
Editora
PERGAMON-ELSEVIER SCIENCE LTD
Autores
SANTANA, Fernanda P. R.
SILVA, Rafael C. da
PONCI, Vitor
PINHEIRO, Aruana J. M. C. R.
CAPERUTO, Luciana C.
CLAUDIO, Samuel R.
RIBEIRO, Daniel A.
Citação
BIOCHEMICAL PHARMACOLOGY, v.180, article ID 114175, 14p, 2020
Resumo
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.
Palavras-chave
Asthma, Dehydrodieugenol, Eugenol, MAPK, STAT
Referências
- Adachi T, 2000, J IMMUNOL, V165, P2198, DOI 10.4049/jimmunol.165.4.2198
- Alam R, 2011, CLIN EXP ALLERGY, V41, P149, DOI 10.1111/j.1365-2222.2010.03658.x
- Barclay LRC, 1997, J WOOD CHEM TECHNOL, V17, P73, DOI 10.1080/02773819708003119
- Bortolomeazzi R, 2010, FOOD CHEM, V118, P256, DOI 10.1016/j.foodchem.2009.04.115
- Bruggemann TR, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.00718
- Chialda L, 2005, RESP RES, V6, DOI 10.1186/1465-9921-6-36
- Pinheiro AJMCR, 2018, J IMMUNOL RES, V2018, DOI 10.1155/2018/6879183
- dos Santos TM, 2018, FRONT PHYSIOL, V9, DOI 10.3389/fphys.2018.01183
- Dullaers M, 2012, J ALLERGY CLIN IMMUN, V129, P635, DOI 10.1016/j.jaci.2011.10.029
- Eynott PR, 2004, IMMUNOLOGY, V112, P446, DOI 10.1111/j.1365-2567.2004.01887.x
- Gavino AC, 2016, ALLERGY, V71, P1684, DOI 10.1111/all.12937
- Goplen N, 2012, FASEB J, V26, P1934, DOI 10.1096/fj.11-196477
- Grecco SS, 2017, PHYTOMEDICINE, V24, P62, DOI 10.1016/j.phymed.2016.11.015
- HANTOS Z, 1992, J APPL PHYSIOL, V72, P168
- Hasegawa T, 2017, EUR CYTOKINE NETW, V28, P8, DOI 10.1684/ecn.2017.0390
- Hernandez-Vazquez L, 2011, J MOL CATAL B-ENZYM, V72, P102, DOI 10.1016/j.molcatb.2011.05.005
- Ito K, 2006, J ALLERGY CLIN IMMUN, V117, P522, DOI 10.1016/j.jaci.2006.01.032
- Khorasanizadeh M, 2017, PHARMACOL THERAPEUT, V174, P112, DOI 10.1016/j.pharmthera.2017.02.024
- Lee SH, 2012, BIOCHEM BIOPH RES CO, V417, P1024, DOI 10.1016/j.bbrc.2011.12.084
- Liu WM, 2008, J ALLERGY CLIN IMMUN, V121, P893, DOI 10.1016/j.jaci.2008.02.004
- Liu YN, 2015, SCI REP-UK, V5, DOI 10.1038/srep11758
- Lopez-Saez MP, 2015, J INVEST ALLERG CLIN, V25, P64
- Magalhaes CB, 2019, RESP PHYSIOL NEUROBI, V259, P30, DOI 10.1016/j.resp.2018.07.001
- Mahapatra SK, 2014, ASIAN PAC J TROP MED, V7, pS391, DOI 10.1016/S1995-7645(14)60264-9
- Masuda A, 2002, J IMMUNOL, V169, P3801, DOI 10.4049/jimmunol.169.7.3801
- Mauad T, 2007, J ALLERGY CLIN IMMUN, V120, P997, DOI 10.1016/j.jaci.2007.06.031
- Maurya AK, 2020, NAT PROD RES, V34, P251, DOI 10.1080/14786419.2018.1528585
- Murakami Y, 2003, BIOCHEM PHARMACOL, V66, P1061, DOI 10.1016/S0006-2952(03)00419-2
- Pan CL, 2015, INFLAMMATION, V38, P1385, DOI 10.1007/s10753-015-0110-8
- Pinheiro NM, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0120441
- Prado VF, 2006, NEURON, V51, P601, DOI 10.1016/j.neuron.2006.08.005
- Quirce S, 2008, ALLERGY, V63, P137, DOI 10.1111/j.1398-9995.2007.01525.x
- Rodrigues LC, 2016, CHEM BIODIVERS, V13, P870, DOI 10.1002/cbdv.201500280
- Santana FPR, 2019, MEDIAT INFLAMM, V2019, DOI 10.1155/2019/1356356
- Toledo AC, 2013, BRIT J PHARMACOL, V168, P1736, DOI 10.1111/bph.12062
- Wakashin H, 2008, AM J RESP CRIT CARE, V178, P1023, DOI 10.1164/rccm.200801-086OC
- WANG JP, 1995, J PHARM PHARMACOL, V47, P857, DOI 10.1111/j.2042-7158.1995.tb05754.x
- Wu HM, 2015, MOL IMMUNOL, V67, P311, DOI 10.1016/j.molimm.2015.06.016
- Yang Q, 2017, CELL MOL BIOL, V63, P71, DOI 10.14715/cmb/2017.63.9.13
- Yu HS, 2010, J KOREAN MED SCI, V25, P829, DOI 10.3346/jkms.2010.25.6.829