title: Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis.
abstract: BACKGROUND
  Schinus terebinthifolius is a species of plant from the Anacardiaceae family, which can be found in different regions of Brazil. Schinus is popularly known as aroeirinha, aroeira-vermelha, or Brazilian pepper. In folk medicine, S. terebinthifolius is used for several disorders, including inflammatory conditions, skin wounds, mucosal membrane ulcers, respiratory problems, gout, tumors, diarrhea and arthritis. According to chemical analyses, gallic acid, methyl gallate and pentagalloylglucose are the main components of hydroalcoholic extracts from S. terebinthifolius leaves. In the present study, we demonstrated the ability of a hydroalcoholic extract to inhibit cell migration in arthritis and investigated the mechanisms underlying this phenomenon.
  
  
  METHODS
  The anti-inflammatory effect of S. terebinthifolius hydroalcoholic leaf extract (ST-70) was investigated in a zymosan-induced experimental model of inflammation. Male Swiss and C57Bl/6 mice received zymosan (100 µg/cavity) via intra-thoracic (i.t.) or intra-articular (i.a.) injection after oral pre-treatment with ST-70. The direct action of ST-70 on neutrophils was evaluated via chemotaxis.
  
  
  RESULTS
  ST-70 exhibited a dose-dependent effect in the pleurisy model. The median effective dose (ED50) was 100mg/kg, which inhibited 70% of neutrophil accumulation when compared with the control group. ST-70 reduced joint diameter and neutrophil influx for synovial tissues at 6h and 24h in zymosan-induced arthritis. Additionally, ST-70 inhibited synovial interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (CXCL1/KC) and Tumor Necrosis Factor (TNF)-α production at 6h and CXCL1/KC and IL-1β production at 24h. The direct activity of ST-70 on neutrophils was observed via the impairment of CXCL1/KC-induced chemotaxis in neutrophils. Oral administration of ST-70 did not induce gastric damage. Daily administration for twenty days did not kill any animals. In contrast, similar administrations of diclofenac induced gastric damage and killed all animals by the fifth day.
  
  
  CONCLUSIONS
  Our results demonstrated significant anti-inflammatory effects of ST-70, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, such as joint inflammation.
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil. Electronic address: ecrosas@fiocruz.br.
authors.forename: Elaine Cruz
authors.initials: EC
authors.lastname: Rosas
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
authors.forename: Luana Barbosa
authors.initials: LB
authors.lastname: Correa
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
authors.forename: Tatiana de Almeida
authors.initials: Tde A
authors.lastname: Pádua
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
authors.forename: Thadeu Estevam Moreira Maramaldo
authors.initials: TE
authors.lastname: Costa
authors.affiliation: Analytical Center, Farmanguinhos, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Mazzei
authors.affiliation: Natural Products Laboratory, Farmanguinhos, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
authors.forename: Alan Patrick
authors.initials: AP
authors.lastname: Heringer
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Bizarro
authors.affiliation: Natural Products Research Center (NPPN), Federal University of Rio de Janeiro (UFRJ), Brazil.
authors.forename: Maria Auxiliadora Coelho
authors.initials: MA
authors.lastname: Kaplan
authors.affiliation: Natural Products Laboratory, Farmanguinhos, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
authors.forename: Maria Raquel
authors.initials: MR
authors.lastname: Figueiredo
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil; National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil. Electronic address: gracahenriques@fiocruz.br.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Henriques
mesh_terms: D027926:Anacardiaceae; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D000431:Ethanol / Q000737:chemistry; D005707:Gallic Acid / Q000494:pharmacology; D006801:Humans; D007719:Knee Joint / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D010998:Pleurisy / Q000188:drug therapy* / Q000276:immunology; D012997:Solvents / Q000737:chemistry; D015054:Zymosan
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010936:Plant Extracts; D012997:Solvents; D000431:Ethanol; D005707:Gallic Acid; D015054:Zymosan
keywords: Arthritis; Gallic acid (PubChem CID: 370); Methyl gallate (PubChem CID: 7428); Neutrophils; Pentagalloylglucose (PubChem CID: 65238); Schinus terebinthifolius Raddi