Literature DB >> 19508397

Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, alpha- and beta-amyrin, in a mouse model of colitis.

C E Vitor1, C P Figueiredo, D B Hara, A F Bento, T L Mazzuco, J B Calixto.   

Abstract

BACKGROUND AND
PURPOSE: 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. EXPERIMENTAL APPROACH: 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). KEY
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 AND IMPLICATIONS: 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.

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Year:  2009        PMID: 19508397      PMCID: PMC2737662          DOI: 10.1111/j.1476-5381.2009.00271.x

Source DB:  PubMed          Journal:  Br J Pharmacol        ISSN: 0007-1188            Impact factor:   8.739


  38 in total

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