Inhibitory effect of reinioside C on monocyte-endothelial cell adhesion induced by oxidized low-density lipoprotein via inhibiting NADPH oxidase/ROS/NF-kappaB pathway.
Monocyte adhesion to activated vascular endothelial cells is the critical event in the initiation of atherosclerosis. Adhesion molecules are inflammatory markers, which are upregulated by oxidized low-density lipoprotein (ox-LDL) and play a pivotal role in atherogenesis. In present study, the effect of reinioside C, a major compound of Polygala fallax Hemsl., on adhesion of monocytes to endothelial cells induced by ox-LDL was investigated. The results showed that incubation of endothelial cells with ox-LDL (100 microg/mL) for 24 h markedly increased the expression of ICAM-1 and P-selectin and enhanced the adhesion of monocytes to endothelial cells. Pretreatment with reinioside C (1, 3, or 10 microM) dose-dependently decreased ox-LDL-induced upregulation of expression of ICAM-1 and P-selectin and the enhanced adhesion of monocytes to endothelial cells. To determine the role of NADPH oxidase/reactive oxygen species (ROS)/nuclear factor-kappaB (NF-kappaB) pathway, endothelial cells were treated with ox-LDL (100 microg/mL) for 2 h, and NADPH oxidase subunit (Nox 2 and p22phox) mRNA expression, intracellular ROS level, and NF-kappaB activity were measured. The results showed that reinioside C attenuated ox-LDL-induced NADPH oxidase subunit (Nox 2 and p22phox) mRNA expression, generation of ROS, and activation of NF-kappaB in endothelial cells in a dose-dependent manner; the two latter effects were inhibited by pyrollidine dithiocarbamate, the inhibitor of NF-kappaB. These findings suggest that reinioside C attenuates ox-LDL-induced expression of adhesion molecules (P-selectin and ICAM-1) and the adhesion of monocytes to endothelial cells by inhibiting NADPH oxidase/ROS/NF-kappaB pathway.
Bai
Yong-Ping
YP
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
Hu
Chang-ping
CP
Chen
Mei-Fang
MF
Xu
Kang-Ping
KP
Tan
Gui-Shan
GS
Shi
Rui-Zhen
RZ
Li
Yuan-Jian
YJ
Zhang
Guo-Gang
GG
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000378:metabolism; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D031801:Polygala / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D008077:Lipoproteins, LDL; D016328:NF-kappa B; D019007:P-Selectin; D017382:Reactive Oxygen Species; D012503:Saponins; C099252:oxidized low density lipoprotein; C530274:reinioside C; D018799:Intercellular Adhesion Molecule-1; D019255:NADPH Oxidases