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
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
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DOI：
10.1016/j.molimm.2013.01.018
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发表时间：
2013-07-01
影响因子：
3.6
通讯作者：
Calixto, Joao B.
中科院分区：
文献类型：
--
作者：
Matos, Israel;Bento, Allisson Freire;Calixto, Joao B.
五环三萜，α， β -amyrin先前已被报道为治疗几种炎症的有效化合物。最近的证据表明，α， β -amyrin通过与大麻素途径的相互作用显示其作用。我们评估了α， β -amyrin在右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎中的抗炎作用，并研究了其作用是否与大麻素系统的相互作用有关。我们的研究结果表明，口服α、β -amyrin预防或治疗性治疗可显著降低疾病活跃性、体重减轻、结肠损伤以及结肠髓过氧化物酶和n -乙酰氨基葡萄糖酶活性。此外，α、β -amyrin降低结肠促炎介质肿瘤坏死因子(TNF)- α、白细胞介素(IL)-1 β和角化细胞来源的趋化因子（CXCL1/KC），同时上调IL-4水平。此外，我们还观察到α、β -amyrin导致粘附分子细胞间粘附分子1 （ICAM-1）、血管细胞粘附分子1 （VCAM-1）、血小板细胞粘附分子1 (PCAM-1) mRNA表达、β(2)-整合素和增殖标志物Ki67、巨噬细胞分子CD68和粘附分子p -选择素的蛋白表达显著降低。有趣的是，我们的研究结果还表明，大麻素受体1 (CB1)，而不是CB2，药物阻断显着逆转了α， β -amyrin在dss诱导的结肠炎中的有益作用。此外，我们的数据表明，内源性大麻素水解酶单甘油酯脂肪酶1 （MGL1）和脂肪酸酰胺水解酶（FAAH）的mRNA表达在α、β -淀粉蛋白处理的小鼠结肠中显著降低。总之，这些结果表明，α， β -amyrin可能对IBD的治疗具有潜在的治疗兴趣，并为潜在的机制提供了新的见解。(C) 2013 Elsevier Ltd.版权所有。
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)-1 beta 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 (CB1), but not CB2, 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. (C) 2013 Elsevier Ltd. All rights reserved.