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- Title
Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, alpha- and beta-amyrin, in a mouse model of colitis.
- Authors
Vitor, CE; Figueiredo, CP; Hara, DB; Bento, AF; Mazzuco, TL; Calixto, JB; Vitor, C E; Figueiredo, C P; Hara, D B; Bento, A F; Mazzuco, T L; Calixto, J B
- Abstract
<bold>Background and Purpose: </bold>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.<bold>Experimental Approach: </bold>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).<bold>Key Results: </bold>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.<bold>Conclusions and Implications: </bold>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.
- Subjects
ANIMAL models of colitis; TERPENES; AMYRIN; PHARMACOLOGY; PHARMACODYNAMICS; SULFONIC acids; CYCLOOXYGENASE 2; VASCULAR endothelial growth factors
- Publication
British Journal of Pharmacology, 2009, Vol 157, Issue 6, p1034
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2009.00271.x