title: Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice.
abstract: OBJECTIVE
  Shikimic acid (SA) is present in a wide variety of plants and microorganisms used in traditional and folk medicine and also is an essential starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Here, we investigated the anti-inflammatory and antinociceptive actions of isolated SA.
  
  
  METHODS
  RAW 264.7 macrophage cells were treated with bacterial LPS (1μg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, and IL-1β content and MAPK (ERK1/2 and p38) activation was evaluated. Besides, the anti-hyperalgesic actions of SA on in vivo model of mechanical hyperalgesia induced by carrageenan (CG), dopamine (DA), TNF-α and prostaglandin (PGE2) were assessed.
  
  
  RESULTS
  In RAW 264.7 cells, SA suppressed LPS-induced decrease in cell viability and nitrite accumulation to control values and inhibited up-regulation of TNF-α (65%) and IL-1β (39%). These effects may be mediated at least in part by inhibition of LPS-induced ERK 1/2 (22%) and p38 (17%) phosphorylation. In mice, SA at 50, 100, and 200mg/kg decreased formalin-induced nociceptive behavior (around 50%) and inhibited the inflammatory nociception induced by TNF-α and PGE2 (50 to 75% each). Moreover, SA (100 and 200mg/kg) significantly attenuated the mechanical hyperalgesia induced by CG and DA (25 to 40% each).
  
  
  CONCLUSIONS
  These results indicate that SA presents anti-inflammatory actions with potential for development of drugs to treat pro-inflammatory and painful conditions.
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Thallita Kelly
authors.initials: TK
authors.lastname: Rabelo
authors.affiliation: Departamento de Educação em Saúde, UFS, Lagarto, SE, Brazil.
authors.forename: Adriana Gibara
authors.initials: AG
authors.lastname: Guimarães
authors.affiliation: Laboratório de Neurociências e Ensaios Farmacêuticos (LANEF), Departamento de Fisiologia, UFS, São Cristóvão, SE, Brazil.
authors.forename: Marlange Almeida
authors.initials: MA
authors.lastname: Oliveira
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Juciano
authors.initials: J
authors.lastname: Gasparotto
authors.affiliation: Laboratorio de Ensaios Farmacêuticos e Toxicidade, Departmento de Farmácia, UFS, São Cristóvão, SE, Brazil.
authors.forename: Mairim Russo
authors.initials: MR
authors.lastname: Serafini
authors.affiliation: Laboratorio de Ensaios Farmacêuticos e Toxicidade, Departmento de Farmácia, UFS, São Cristóvão, SE, Brazil.
authors.forename: Adriano Antunes
authors.initials: AA
authors.lastname: de Souza Araújo
authors.affiliation: Laboratório de Neurociências e Ensaios Farmacêuticos (LANEF), Departamento de Fisiologia, UFS, São Cristóvão, SE, Brazil.
authors.forename: Lucindo José
authors.initials: LJ
authors.lastname: Quintans-Júnior
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: José Cláudio Fonseca
authors.initials: JCF
authors.lastname: Moreira
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil. Electronic address: daniel.gelain@ufrgs.br.
authors.forename: Daniel Pens
authors.initials: DP
authors.lastname: Gelain
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy*; D007111:Immunity, Cellular / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D053139:Oseltamivir / Q000627:therapeutic use; D000067996:RAW 264.7 Cells; D012765:Shikimic Acid / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D053139:Oseltamivir; D012765:Shikimic Acid; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cytokines; Inflammation; Mechanical hyperalgesia; Nociception; Raw 264.7; Shikimic acid