title: Modulatory effect of Senecio brasiliensis (Spreng) Less. in a murine model of inflammation induced by carrageenan into the pleural cavity.
abstract: BACKGROUND
  Senecio brasiliensis (Spreng) Less (S. brasiliensis), known as "Flor-das-almas", "Margaridinha" or "Maria mole", is used in folk medicine as an anti-inflammatory and to treat gastric ulcers and stomach pain. While the Senecio genus has been widely studied for its pharmacological activities to support its use in traditional medicine, few studies focus on the anti-inflammatory activities of the species.
  
  
  OBJECTIVE
  To investigate the anti-inflammatory activities of S. brasiliensis, a specie native to Brazil, using a murine model of pleurisy induced by carrageenan.
  
  
  METHODS
  The flowers of S. brasiliensis were air-dried for 3 days and subjected to ethanol (96%) extraction for 7 days to obtain the crude extract (CE). The CE was subjected to acid-base extraction to obtain the alkaloid fraction (AF). The hexane (HEX), dichloromethane (DCM) and ethyl acetate (EtOAc) fractions were obtained by extracting from CE with different solvents. The alkaloids senecionine (Sen), integerrimine (Int) and senecionine N-oxide were obtained from AF by chromatographic fractionation and a mixture of 1,4-, 3,4-, 3,5- and 4,5-dicaffeoylquinic acids (DCQs) were obtained from the EtOAc fraction. The isolated alkaloids were identified through spectroscopic analysis of IR, NMR and LC-MS coupled with electrospray ionization mass spectrometry (ESI-MS), and the dicaffeoylquinic acids through the hierarchical key method. Swiss mice were used in the in vivo experiments. We evaluated the effect of the CE, its derived fractions (AF, HEX, DCM and EtOAc), and the isolated compounds (Sen, Int, N-oxide senecionine, and DCQs) on: leukocyte migration, exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, and tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 17A levels in the fluid leakage from the pleural cavity using a mouse model of pleurisy induced by carrageenan. The effects of the isolated compounds, Sen, Int, N-oxide senecionine and DCQs, were also analyzed for their ability to inhibit p65 phosphorylation (p-p65) in the nuclear factor-kappa B (NF-κB) pathway in the lung tissue. MPO and ADA were analyzed by colorimetric assays, and the cytokines and protein p65 levels were determined using an enzyme immunoassay (EIA).
  
  
  RESULTS
  The CE, its EtOAc and AF fractions, and its isolated compounds (Sen, Int and DCQs), significantly reduced leukocyte migration (P < 0.05), MPO and ADA activities (P < 0.01), and TNF-α (P < 0.05), and IL-17A levels (P < 0.01). The CE, the EtOAc and AF fractions, and the DCQs also decreased IL-1β levels (P < 0.01). The isolated compounds, Sen, Int and the DCQs, inhibited p65 phosphorylation (NF-κB) (P < 0.05).
  
  
  CONCLUSIONS
  This study demonstrated that S. brasiliensis has important anti-inflammatory properties that are capable of inhibiting activated leukocytes by decreasing neutrophil migration. This effect may be attributed to the inhibition of pro-inflammatory cytokines and the reduction of the NF-κB pathway. The compounds Sen, Int, and DCQs may be responsible for the anti-inflammatory actions of S. brasiliensis.
authors.affiliation: Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-970, SC, Brazil.
authors.forename: Renata Rodrigues
authors.initials: RR
authors.lastname: de Souza
authors.affiliation: Department of Chemistry, Center of Physical and Mathematical Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
authors.forename: Lizandra Czermainski
authors.initials: LC
authors.lastname: Bretanha
authors.affiliation: Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-970, SC, Brazil.
authors.forename: Eduardo Monguilhott
authors.initials: EM
authors.lastname: Dalmarco
authors.affiliation: Department of Chemistry, Center of Physical and Mathematical Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzolatti
authors.affiliation: Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-970, SC, Brazil. Electronic address: tania.frode@ufsc.br.
authors.forename: Tânia Silvia
authors.initials: TS
authors.lastname: Fröde
mesh_terms: D000243:Adenosine Deaminase / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan; D016207:Cytokines / Q000276:immunology; D035264:Flowers; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000276:immunology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D035422:Pleural Cavity / Q000166:cytology / Q000276:immunology; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D012674:Senecio; D051996:Transcription Factor RelA / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010936:Plant Extracts; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D002351:Carrageenan; D009195:Peroxidase; D000243:Adenosine Deaminase
keywords: Anti-inflammatory effect; Cytokines; Dicaffeoylquinic acid; NF-Kappa B pathway; Pyrrolizidine alkaloids; Senecio brasiliensis