Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, α‐ and β‐amyrin, in a mouse model of colitis

• Published in: British journal of pharmacology 2009-07, Vol.157 (6), p.1034-1044
• Main Authors: Vitor, CE, Figueiredo, CP, Hara, DB, Bento, AF, Mazzuco, TL, Calixto, JB
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cAMP response element‐binding protein; Colitis - chemically induced; Colitis - drug therapy; Colitis - pathology; cyclooxygenase‐2; Disease Models, Animal; Drug Therapy, Combination; Gastroenterology. Liver. Pancreas. Abdomen; inflammation; inflammatory bowel disease; interleukins; Male; Medical sciences; Mice; mouse colitis; nuclear factor‐κB; Oleanolic Acid - administration & dosage; Oleanolic Acid - analogs & derivatives; Other diseases. Semiology; Pentacyclic Triterpenes - administration & dosage; Pharmacology. Drug treatments; Research Papers; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Trinitrobenzenesulfonic Acid - toxicity; vascular endothelial growth factor; α,β‐amyrin
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2009.00271.x

Background and purpose:  α‐ and β‐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 α‐ and β‐amyrin (α,β‐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 α,β‐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‐κB (NF‐κB) 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 α,β‐amyrin (3 mg·kg−1, i.p.) or dexamethasone (1 mg·kg−1, s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. α,β‐Amyrin, like dexamethasone, significantly diminished interleukin (IL)‐1β levels and partially restored IL‐10 levels in colon tissues 72 h after colitis induction, but only α,β‐amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX‐2 at 24 h and that of phospho‐NF‐κB and phospho‐CREB (peaking at 6 h) after colitis induction were consistently inhibited by both α,β‐amyrin and dexamethasone. Conclusions and implications:  Systemic administration of α,β‐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‐κB and CREB‐signalling pathways. Taken together, our data suggest a potential use of α,β‐amyrin to control inflammatory responses in bowel disease.