Matos_2013_Mol.Immunol_54_482

The pentacyclic triterpene alpha,beta-amyrin has been previously reported as an effective compound in the treatment of several inflammatory conditions. Recent evidence indicates that alpha,beta-amyrin displayed its effects through interaction with the cannabinoid pathway. We assessed the anti-inflammatory effects of the alpha,beta-amyrin in the dextran sulfate sodium (DSS)-induced colitis in mice and investigated whether its effects were associated with the interaction with the cannabinoid system. Our results showed that the oral preventive or therapeutic treatment with alpha,beta-amyrin significantly reduced disease activity, body weight loss, colonic damage, as well as colonic myeloperoxidase and N-acetylglucosaminidase activities. Moreover, alpha,beta-amyrin decreases the colonic pro-inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and keratinocyte-derived chemokine (CXCL1/KC), while up-regulating the IL-4 levels. Additionally, we also observed that the alpha,beta-amyrin caused a significant reduction of the adhesion molecules mRNA expression for intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), platelet cell adhesion molecule 1 (PCAM-1), beta(2)-integrin and protein expression for proliferation marker Ki67, the macrophage molecule CD68 and for adhesion molecule P-selectin. Interestingly, our results also showed that the cannabinoid receptor 1 (CB(1)), but not CB(2), pharmacological blockade significantly reversed the beneficial effects of alpha,beta-amyrin in DSS-induced colitis. Besides, our data demonstrated that mRNA expression for both the endocannabinoid hydrolase monoglyceride lipase 1 (MGL1) and fatty acid amide hydrolase (FAAH) were significantly reduced in the colon of alpha,beta-amyrin-treated mice. Altogether, these results suggest that the alpha,beta-amyrin might possess potential therapeutic interest for the treatment of IBD, and also provide new insights for the underlying mechanisms.