title: Cinnamaldehyde modulates LPS-induced systemic inflammatory response syndrome through TRPA1-dependent and independent mechanisms.
abstract: Cinnamaldehyde is a natural essential oil suggested to possess anti-bacterial and anti-inflammatory properties; and to activate transient receptor potential ankyrin 1 (TRPA1) channels expressed on neuronal and non-neuronal cells. Here, we investigated the immunomodulatory effects of cinnamaldehyde in an in vivo model of systemic inflammatory response syndrome (SIRS) induced by lipopolysaccharide. Swiss mice received a single oral treatment with cinnamaldehyde 1 h before LPS injection. To investigate whether cinnamaldehyde effects are dependent on TRPA1 activation, animals were treated subcutaneously with the selective TRPA1 antagonist HC-030031 5 min prior to cinnamaldehyde administration. Vehicle-treated mice were used as controls. Cinnamaldehyde ameliorated SIRS severity in LPS-injected animals. Diminished numbers of circulating mononuclear cells and increased numbers of peritoneal mononuclear and polymorphonuclear cell numbers were also observed. Cinnamaldehyde augmented the number of peritoneal Ly6C(high) and Ly6C(low) monocyte/macrophage cells in LPS-injected mice. Reduced levels of nitric oxide, plasma TNFα and plasma and peritoneal IL-10 were also detected. Additionally, IL-1β levels were increased in the same animals. TRPA1 antagonism by HC-030031 reversed the changes in the number of circulating and peritoneal leukocytes in cinnamaldehyde-treated animals, whilst increasing the levels of peritoneal IL-10 and reducing peritoneal IL-1β. Overall, cinnamaldehyde modulates SIRS through TRPA1-dependent and independent mechanisms.
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Saulo J F
authors.initials: SJF
authors.lastname: Mendes
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Fernanda I A B
authors.initials: FIAB
authors.lastname: Sousa
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Domingos M S
authors.initials: DMS
authors.lastname: Pereira
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Thiago A F
authors.initials: TAF
authors.lastname: Ferro
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Ione C P
authors.initials: ICP
authors.lastname: Pereira
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Bruna L R
authors.initials: BLR
authors.lastname: Silva
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Aruanã J M C R
authors.initials: AJMCR
authors.lastname: Pinheiro
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Adriana Q S
authors.initials: AQS
authors.lastname: Mouchrek
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil; Departamento de Patologia, Universidade Federal do Maranhão, São Luís, Maranhão, Brazil.
authors.forename: Valério
authors.initials: V
authors.lastname: Monteiro-Neto
authors.affiliation: Departamento de Farmacologia, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Soraia K P
authors.initials: SKP
authors.lastname: Costa
authors.affiliation: Departamento de Fisiologia, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: José L M
authors.initials: JLM
authors.lastname: Nascimento
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil.
authors.forename: Marcos A G
authors.initials: MAG
authors.lastname: Grisotto
authors.affiliation: Departamento de Biotecnologia Farmacêutica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: da Costa
authors.affiliation: Programa de Pós-Graduação, Universidade CEUMA, São Luís, Maranhão, Brazil. Electronic address: elizabeth.soares@ceuma.br.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Fernandes
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000171:Acrolein / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002935:Cinnamomum zeylanicum / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D011247:Pregnancy; D011687:Purines / Q000494:pharmacology; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011687:Purines; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D016753:Interleukin-10; D000171:Acrolein; C012843:cinnamaldehyde
keywords: Cinnamaldehyde; Sepsis; Systemic inflammatory response syndrome (SIRS); TRPA1