title: Anti-inflammatory effect of triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene obtained from Combretum leprosum Mart & Eich in mice.
abstract: BACKGROUND
  The 3β, 6β, 16β-trihydroxylup-20(29)-ene (TTHL) is a pentacyclic triterpene obtained from a medicinal plant named Combretum leprosum. In folk medicine, this plant is used to treat several diseases associated with inflammation and pain. We previously demonstrated that TTHL presents a significant antinociceptive effect, suggesting the involvement of the glutamatergic system.
  
  
  OBJECTIVE
  This study was designed to investigate the effect of TTHL on nociception and vascular permeability induced by acetic acid. We also evaluated the effect of TTHL on carrageenan-induced peritonitis and the levels of cytokines (interleukin 1-β [IL-1β], tumor necrosis factor α [TNF-α] and interleukin 10 [IL-10]) on peritoneal fluid.
  
  
  METHODS
  TTHL was administered orally by intra-gastric gavage (i.g.) 60 min prior to experimentation. Abdominal contractions and vascular permeability were induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also investigated whether TTHL decreases carrageenan-induced peritonitis (750 μg/cavity) by measuring leukocyte migration and vascular permeability. In addition, we evaluated the effects of TTHL on TNF-α, IL-1β and IL-10 release induced by carrageenan on peritoneal fluid. The levels of these cytokines were measured by ELISA.
  
  
  RESULTS
  TTHL (0.01-10 mg/kg) administered by intra-gastric (i.g.) gavage inhibited (69±3%) acetic acid-induced abdominal constrictions, with an ID₅₀ of 0.15 (0.03-0.8) mg/kg. TTHL (10mg/kg) also reduced the leukocyte infiltration induced by acetic acid, with an inhibition of 59±9 but had no effect on abdominal vascular permeability. In addition, indomethacin (10 mg/kg, i.p.) reduced the nociceptive behavior (92±1%), total leukocyte migration (29±3%) and capillary permeability (71±3%) induced by acetic acid. While the glucocorticoid dexamethasone (2 mg/kg, s.c.) reduced partially but significantly the nociception (31±1%), besides to promote a marked reduction on total leukocyte migration (60±2%) to the peritoneal cavity caused by acetic acid. In a model of peritonitis induced by carrageenan, TTHL also reduced total leukocyte migration, mainly neutrophils (inhibition of 84±3% and 85±2% at 30 mg/kg and 100 mg/kg, respectively). Likewise, dexamethasone (0.5 mg/kg, i.p.) resulted in an inhibition of 93±3%. Nevertheless, carrageenan-induced abdominal vascular permeability was reduced by dexamethasone but was not altered by TTHL. Furthermore, dexamethasone and TTHL significantly reduced the TNF-α and IL-1β levels in peritoneal fluid, whereas the IL-10 levels were unchanged.
  
  
  CONCLUSIONS
  Altogether, our data confirm the antinociceptive effect of TTHL and demonstrate its effect in inflammatory animal models, providing novel data about this compound, which could be useful as an anti-inflammatory drug.
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis, SC, Brazil.
authors.forename: Daniela T
authors.initials: DT
authors.lastname: Longhi-Balbinot
authors.forename: Débora
authors.initials: D
authors.lastname: Lanznaster
authors.forename: Cristiane Hatsuko
authors.initials: CH
authors.lastname: Baggio
authors.forename: Morgana Duarte
authors.initials: MD
authors.lastname: Silva
authors.forename: Celeste Heiseke
authors.initials: CH
authors.lastname: Cabrera
authors.forename: Valdir A
authors.initials: VA
authors.lastname: Facundo
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001202:Ascitic Fluid / Q000276:immunology; D002199:Capillary Permeability; D002351:Carrageenan; D029765:Combretum; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008517:Phytotherapy; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C510987:3beta,6beta,16beta-trihidroxilup-20(29)-ene; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D014315:Triterpenes; D002351:Carrageenan; D019342:Acetic Acid