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.

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.

Matos I ，Bento AF ，Marcon R ，Claudino RF ，Calixto JB ... -  《-》

Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis.

Marcon R ，Bento AF ，Dutra RC ，Bicca MA ，Leite DF ，Calixto JB ... -  《-》

The anti-inflammatory and antioxidant effects of bergamot juice extract (BJe) in an experimental model of inflammatory bowel disease.

The beneficial properties of the flavonoid fraction of bergamot juice (BJe) have been raising interest and have been the subject of recent studies, considering the potentiality of its health promoting substances. Flavonoids have demonstrated radical-scavenging and anti-inflammatory activities. The aim of the present study was to examine the effects of BJe in mice subjected to experimental colitis. Colitis was induced in mice by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). BJe was administered daily orally (at 5, 10 and 20 mg/kg). Four days after DNBS administration, colon nuclear factor NF-κB translocation and MAP kinase phospho-JNK activation were increased as well as cytokine production such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Neutrophil infiltration, by myeloperoxidase (MPO) activity, in the mucosa was associated with up-regulation of adhesion molecules (ICAM-1 and P-selectin). Immunohistochemistry for nitrotyrosine and poly ADP-ribose (PAR) also showed an intense staining in the inflamed colon. Treatment with BJe decreased the appearance of diarrhea and body weight loss. This was associated with a reduction in colonic MPO activity. BJe reduced nuclear NF-κB translocation, p-JNK activation, the pro-inflammatory cytokines release, the appearance of nitrotyrosine and PAR in the colon and reduced the up-regulation of ICAM-1 and P-selectin. In addition, colon inflammation was also associated with apoptotic damage. Treatment with BJe caused a decrease of pro-apoptotic Bax expression and an increase of anti-apoptotic Bcl-2 expression. The results of this study suggested that administration of BJe induced, partly specified, anti-inflammatory mechanisms, which potentially may be beneficial for the treatment of IBD in humans.

Impellizzeri D ，Bruschetta G ，Di Paola R ，Ahmad A ，Campolo M ，Cuzzocrea S ，Esposito E ，Navarra M ... -  《-》

The detrimental effect of nitric oxide on tissue is associated with inflammatory events in the vascular endothelium and neutrophils in mice with dextran sodium sulfate-induced colitis.

Yasukawa K ，Tokuda H ，Tun X ，Utsumi H ，Yamada K ... -  《-》

T cell-associated CD18 but not CD62L, ICAM-1, or PSGL-1 is required for the induction of chronic colitis.

Ostanin DV ，Furr KL ，Pavlick KP ，Gray L ，Kevil CG ，Shukla D ，D'Souza D ，Hoffman JM ，Grisham MB ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY》