Oridonin inhibits vascular inflammation by blocking NF-κB and MAPK activation
Oridonin inhibits vascular inflammation by blocking NF-κB and MAPK activation
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DOI：
10.1016/j.ejphar.2018.02.044
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发表时间：
2018-05-05
影响因子：
5
通讯作者：
Liang, Jiang
中科院分区：
文献类型：
--
作者：
Huang, Weichen;Huang, Mingcheng;Liang, Jiang
冬凌草甲素是从植物冬凌草中分离得到的一种活性二萜类化合物，具有多种药理活性，包括抗氧化、抗肿瘤和抗炎作用。本研究旨在探讨冬凌草甲素对内皮细胞炎症的调节作用及其机制。白细胞-内皮细胞粘附试验检测内皮细胞-单核细胞相互作用。Western blot检测蛋白表达。免疫荧光法检测NF-κ B B p65易位。采用急性肺部炎症模型评价白细胞浸润情况。冬凌草甲素能显著降低内皮细胞与白细胞的粘附和白细胞的游走。冬凌草甲素显著抑制TNF-α诱导的内皮粘附分子（细胞间粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）和E-选择素）和促炎细胞因子（IL-6、IL-8和单核细胞趋化蛋白-1（MCP-1））的表达。冬凌草甲素对急性肺损伤小鼠白细胞的穿透有抑制作用。冬凌草甲素还能抑制TNF-α激活的MAPK和核因子κ B（NF-κ B）的激活。我们的研究结果表明，冬凌草甲素在内皮细胞中具有抗炎特性，至少部分地，通过抑制MAPK和NF-κ B活化，这可能具有潜在的治疗炎症性血管疾病的用途。
Oridonin, an active diterpenoid compound isolated from the plant Rabdosia Rrubescens, has various pharmacological activities, including antioxidant, anti-tumor capacities and anti-inflammation. In the present study, we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism. Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay. The protein expression was measured by Western blot. NF-kappa B p65 translocation was measured by immunofluorescence. Acute lung inflammation model was used to evaluate leukocyte infiltration in vivo. The endothelial-leukocyte adhesion and the leukocyte transmigration were profoundly reduced by oridonin. Oridonin dramatically inhibited the expression of TNF-alpha-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) and E-selectin) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1(MCP-1)). Oridonin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, Oridonin also suppressed the TNF-alpha-activated MAPK and Nuclear factor kappa B (NF-kappa B) activation. Our results suggest that oridonin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of MAPK and NF-kappa B activation, which may have a potential therapeutic use for inflammatory vascular diseases.