Liang Jiang, Yuan Shiwen, Wang Xiaohua, Lei Yan, Zhang Xuemei, Huang Mingcheng, Ouyang Hui
Collaborative Innovation Center of Miao Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China; Department of Rheamatology and Hematology, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
Int Immunopharmacol. 2020 Mar 2;82:106326. doi: 10.1016/j.intimp.2020.106326.
Pristimerin is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been described. In this study, to investigate the therapeutic mechanism of pristimerin, we examined the effect of pristimerin on TNF-α-induced endothelial inflammatory response both in vitro and in vivo.
Leukocyte-endothelium Adhesion Assay was use to evaluate the endothelial cell-monocyte interaction. Western blotting was used to confirm protein expression. NF-κB p65 nuclear translocation in endothelial cells was detected using immunofluorescent microscopy. In vivo leukocyte infiltration was evaluated using acute lung inflammation model.
Pristimerin profoundly inhibited TNF-α-induced adhesion of monocytes to human endothelial cells and the leukocyte transmigration. Pristimerin dramatically inhibited the expression of TNF-α-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1)). Pristimerin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, pristimerin also suppressed the TNF-α-activated Nuclear factor kappa B (NF-κB) activation.
Pristimerin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of NF-κB activation, which may have a potential therapeutic effects for inflammatory vascular diseases.
已知蛇葡萄素具有抗癌和抗炎活性；然而，其治疗机制尚未见报道。在本研究中，为了探究蛇葡萄素的治疗机制，我们在体外和体内检测了蛇葡萄素对肿瘤坏死因子-α（TNF-α）诱导的内皮细胞炎症反应的影响。
采用白细胞-内皮细胞黏附试验评估内皮细胞与单核细胞的相互作用。利用蛋白质印迹法确认蛋白表达。采用免疫荧光显微镜检测内皮细胞中核因子κB（NF-κB）p65的核转位。使用急性肺炎症模型评估体内白细胞浸润情况。
蛇葡萄素显著抑制TNF-α诱导的单核细胞与人内皮细胞的黏附以及白细胞迁移。蛇葡萄素显著抑制TNF-α诱导的内皮细胞黏附分子（细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1））以及促炎细胞因子（白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和单核细胞趋化蛋白-1（MCP-1））的表达。蛇葡萄素抑制急性肺损伤小鼠模型中白细胞的浸润。此外，蛇葡萄素还抑制TNF-α激活的NF-κB活化。
蛇葡萄素在内皮细胞中具有抗炎特性，至少部分是通过抑制NF-κB活化实现的，这可能对炎症性血管疾病具有潜在治疗作用。
