title: Antinociceptive and anti-arthritic effects of kramecyne.
abstract: OBJECTIVE
  The aim of this study was to evaluate the antinociceptive (acute assays) and anti-inflammatory (chronic assays) effects of kramecyne (KACY), a peroxide isolated from Krameria cytisoides.
  
  
  METHODS
  The antinociceptive activity of KACY was evaluated using the hot plate, acetic acid and formalin tests. The effects of KACY on heat-induced hemolysis in rat erythrocytes were also evaluated. The in vivo anti-inflammatory assays were performed using the chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema and carrageenan-kaolin induced arthritis (CKIA). In the CKIA model, the hot plate test was performed, serum samples were obtained for the quantitation of pro-inflammatory (IL-1β, IL-6, IL-12 and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines.
  
  
  RESULTS
  KACY possess antinociceptive effects with comparable activity to naproxen (NPX). KACY inhibited hemolysis (EC50 = 180 μg/mL), in comparison to the untreated group and with a higher potency than NPX (EC50 = 263 μg/mL). KACY at 50 mg/kg decreased inflammation by 38% (chronic TPA-induced edema model) and by 26% (CKIA model), in comparison with the vehicle group and with similar activity to the positive controls 8 mg/kg indomethacin (IND) and 1 mg/kg methotrexate (MTX), respectively. In the CKIA model, KACY increased the release of anti-inflammatory (IL-4 and IL-10) cytokines but reduced the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 and TNF-α). KACY at 50 and 100 mg/kg showed antinociceptive effects by 27% and 23%, respectively, in mice with mono-arthritis.
  
  
  CONCLUSIONS
  KACY might be a good alternative for the treatment of rheumatoid arthritis (RA) due its antinociceptive and anti-inflammatory activities.
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana - Xochimilco, Mexico.
authors.forename: Angel Josabad
authors.initials: AJ
authors.lastname: Alonso-Castro
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana - Xochimilco, Mexico.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Zavala-Sánchez
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana - Xochimilco, Mexico.
authors.forename: Julia
authors.initials: J
authors.lastname: Pérez-Ramos
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana - Xochimilco, Mexico.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Sánchez-Mendoza
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana - Xochimilco, Mexico. Electronic address: msperez@correo.xoc.uam.mx.
authors.forename: Salud
authors.initials: S
authors.lastname: Pérez-Gutiérrez
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004910:Erythrocyte Membrane / Q000187:drug effects; D004988:Ethers, Cyclic / Q000627:therapeutic use*; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D031326:Krameriaceae / Q000737:chemistry; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010545:Peroxides / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004988:Ethers, Cyclic; D010545:Peroxides; C000596369:kramecyne
keywords: Carrageenan; Cytokines; Kaolin; Kramecyne; Methotrexate; Monoarthritis