Preventive and therapeutic oral administration of the pentacyclic triterpene α,β-amyrin ameliorates dextran sulfate sodium-induced colitis in mice: the relevance of cannabinoid system.

Abstract

The pentacyclic triterpene α,β-amyrin has been previously reported as an effective compound in the treatment of several inflammatory conditions. Recent evidence indicates that α,β-amyrin displayed its effects through interaction with the cannabinoid pathway. We assessed the anti-inflammatory effects of the α,β-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 α,β-amyrin significantly reduced disease activity, body weight loss, colonic damage, as well as colonic myeloperoxidase and N-acetylglucosaminidase activities. Moreover, α,β-amyrin decreases the colonic pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin (IL)-1β and keratinocyte-derived chemokine (CXCL1/KC), while up-regulating the IL-4 levels. Additionally, we also observed that the α,β-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), β(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 α,β-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 α,β-amyrin-treated mice. Altogether, these results suggest that the α,β-amyrin might possess potential therapeutic interest for the treatment of IBD, and also provide new insights for the underlying mechanisms.

• Authors: Israel Matos, Allisson Freire Bento, Rodrigo Marcon, Rafaela Franco Claudino, João B Calixto
• Journal: Molecular immunology (Mol Immunol) Vol. 54 Issue 3-4 Pg. 482-92 (Jul 2013) ISSN: 1872-9142 [Electronic] England
• PMID: 23454360 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• Asialoglycoproteins
• CD18 Antigens
• CD68 protein, mouse
• Cannabinoids
• Cell Adhesion Molecules
• Chemokines
• Clec10a protein, mouse
• Interleukin-1beta
• Ki-67 Antigen
• Lectins, C-Type
• Membrane Proteins
• P-Selectin
• RNA, Messenger
• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• keratinocyte-derived chemokines
• Interleukin-4
• Oleanolic Acid
• Dextran Sulfate
• Peroxidase
• Amidohydrolases
• fatty-acid amide hydrolase
• beta-amyrin

Topics

• Administration, Oral
• Amidohydrolases (genetics, metabolism)
• Animals
• Antigens, CD (genetics, metabolism)
• Antigens, Differentiation, Myelomonocytic (genetics, metabolism)
• Asialoglycoproteins (genetics, metabolism)
• Body Weight (drug effects, genetics)
• CD18 Antigens (genetics, metabolism)
• Cannabinoids (genetics, metabolism)
• Cell Adhesion Molecules (genetics, metabolism)
• Chemokines (genetics, metabolism)
• Colitis (chemically induced, drug therapy, genetics, metabolism)
• Colon (drug effects, metabolism)
• Dextran Sulfate
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Interleukin-1beta (genetics, metabolism)
• Interleukin-4 (genetics, metabolism)
• Ki-67 Antigen (genetics, metabolism)
• Lectins, C-Type (genetics, metabolism)
• Male
• Membrane Proteins (genetics, metabolism)
• Mice
• Oleanolic Acid (analogs & derivatives, pharmacology)
• P-Selectin (genetics, metabolism)
• Peroxidase (genetics, metabolism)
• RNA, Messenger (genetics)
• Receptor, Cannabinoid, CB1 (genetics, metabolism)
• Receptor, Cannabinoid, CB2 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Up-Regulation (drug effects, genetics)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)