Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, SC, Brazil.
Br J Pharmacol. 2009 Jul;157(6):1034-44. doi: 10.1111/j.1476-5381.2009.00271.x. Epub 2009 Jun 5.
alpha- and beta-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 alpha- and beta-amyrin (alpha,beta-amyrin) on an experimental model of colitis in mice.
Colitis was induced in Swiss male mice by trinitrobenzene sulphonic acid (TNBS) and followed up to 72 h; animals were treated systemically with alpha,beta-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-kappaB (NF-kappaB) and phospho-cyclic AMP response element-binding protein (CREB).
TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of inflammatory mediators. Treatment with alpha,beta-amyrin (3 mg x kg(-1), i.p.) or dexamethasone (1 mg x kg(-1), s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. alpha,beta-Amyrin, like dexamethasone, significantly diminished interleukin (IL)-1beta levels and partially restored IL-10 levels in colon tissues 72 h after colitis induction, but only alpha,beta-amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX-2 at 24 h and that of phospho-NF-kappaB and phospho-CREB (peaking at 6 h) after colitis induction were consistently inhibited by both alpha,beta-amyrin and dexamethasone.
Systemic administration of alpha,beta-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-kappaB and CREB-signalling pathways. Taken together, our data suggest a potential use of alpha,beta-amyrin to control inflammatory responses in bowel disease.
α-和β-香树脂醇是植物中存在的五环三萜，具有显著的抗炎作用。在这里，我们评估了 α-和 β-香树脂醇（α，β-香树脂醇）混合物对小鼠结肠炎实验模型的影响。
用三硝基苯磺酸（TNBS）诱导瑞士雄性小鼠结肠炎，并持续观察 72 小时；动物通过系统给予 α，β-香树脂醇、地塞米松或载体进行治疗。在结肠中评估宏观和微观损伤、髓过氧化物酶活性和细胞因子水平。对组织学切片进行环氧化酶-2（COX-2）、血管内皮生长因子、磷酸化 p65 核因子-κB（NF-κB）和磷酸化 cAMP 反应元件结合蛋白（CREB）的免疫染色。
TNBS 诱导的结肠炎与组织损伤、中性粒细胞浸润和炎症介质的时间依赖性增加有关。用 α，β-香树脂醇（3 mg x kg(-1)，腹腔注射）或地塞米松（1 mg x kg(-1)，皮下注射）治疗可一致改善组织损伤评分并消除多形核细胞浸润。α，β-香树脂醇与地塞米松一样，显著降低结肠炎诱导后 72 小时结肠组织中白细胞介素（IL）-1β水平，并部分恢复 IL-10 水平，但只有 α，β-香树脂醇通过免疫组织化学降低血管内皮生长因子的表达。结肠炎诱导后 24 小时结肠 COX-2 的表达和 6 小时后磷酸化 NF-κB 和磷酸化 CREB（峰值）的表达均被 α，β-香树脂醇和地塞米松一致抑制。
系统给予 α，β-香树脂醇对 TNBS 诱导的结肠炎有明显而迅速的抑制作用，这与局部抑制炎症细胞因子和 COX-2 水平有关，可能通过抑制 NF-κB 和 CREB 信号通路。综上所述，我们的数据表明 α，β-香树脂醇具有控制肠道疾病炎症反应的潜力。
