title: Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, alpha- and beta-amyrin, in a mouse model of colitis.
abstract: OBJECTIVE
  alpha- and beta-amyrin are pentacyclic triterpenes found in plants and are known to exhibit pronounced anti-inflammatory effects. Here, we evaluated the effects of a 1:1 mixture of alpha- and beta-amyrin (alpha,beta-amyrin) on an experimental model of colitis in mice.
  
  
  METHODS
  Colitis was induced in Swiss male mice by trinitrobenzene sulphonic acid (TNBS) and followed up to 72 h; animals were treated systemically with alpha,beta-amyrin, dexamethasone or vehicle. Macro- and microscopic damage, myeloperoxidase activity and cytokine levels were assessed in colons. Histological sections were immunostained for cyclooxygenase-2 (COX-2), vascular endothelial growth factor, phospho-p65 nuclear factor-kappaB (NF-kappaB) and phospho-cyclic AMP response element-binding protein (CREB).
  
  
  RESULTS
  TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of inflammatory mediators. Treatment with alpha,beta-amyrin (3 mg x kg(-1), i.p.) or dexamethasone (1 mg x kg(-1), s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. alpha,beta-Amyrin, like dexamethasone, significantly diminished interleukin (IL)-1beta levels and partially restored IL-10 levels in colon tissues 72 h after colitis induction, but only alpha,beta-amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX-2 at 24 h and that of phospho-NF-kappaB and phospho-CREB (peaking at 6 h) after colitis induction were consistently inhibited by both alpha,beta-amyrin and dexamethasone.
  
  
  CONCLUSIONS
  Systemic administration of alpha,beta-amyrin exerted a marked and rapid inhibition of TNBS-induced colitis, related to the local suppression of inflammatory cytokines and COX-2 levels, possibly via inhibition of NF-kappaB and CREB-signalling pathways. Taken together, our data suggest a potential use of alpha,beta-amyrin to control inflammatory responses in bowel disease.
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, SC, Brazil.
authors.forename: C E
authors.initials: CE
authors.lastname: Vitor
authors.forename: C P
authors.initials: CP
authors.lastname: Figueiredo
authors.forename: D B
authors.initials: DB
authors.lastname: Hara
authors.forename: A F
authors.initials: AF
authors.lastname: Bento
authors.forename: T L
authors.initials: TL
authors.lastname: Mazzuco
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D053978:Pentacyclic Triterpenes / Q000008:administration & dosage*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D053978:Pentacyclic Triterpenes; D009828:Oleanolic Acid; D014302:Trinitrobenzenesulfonic Acid; C036380:beta-amyrin