Jiang Liang1, Shiwen Yuan2, Xiaohua Wang3, Yan Lei3, Xuemei Zhang3, Mingcheng Huang4, Hui Ouyang5. 1. 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. 2. Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China. 3. Department of Nephrology,Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, ShenZhen, Guandong, China. 4. Department of Nephrology,Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, ShenZhen, Guandong, China. Electronic address: ouyh3@mail2.sysu.edu.cn. 5. Department of Digestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, ShenZhen, Guandong, China. Electronic address: huangcongen2018@sina.com.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: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. METHODS: 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. RESULTS: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 injurymice model. Furthermore, pristimerin also suppressed the TNF-α-activated Nuclear factor kappa B (NF-κB) activation. CONCLUSIONS: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.