Ophiopogonin D prevents H2O2-induced injury in primary human umbilical vein endothelial cells

被引:128
作者
Qian, Jinchun [1 ]
Jiang, Fengrong [2 ]
Wang, Bin [1 ]
Yu, Yang [1 ]
Zhang, Xu [2 ]
Yin, Zhimin [1 ]
Liu, Chang [1 ]
机构
[1] Nanjing Normal Univ, Coll Life Sci, Jiangsu Key Lab Mol & Med Biotechnol, Nanjing, Peoples R China
[2] Nanjing Univ Tradit Chinese Med, Coll Pharm, Nanjing, Peoples R China
基金
美国国家科学基金会;
关键词
Endothelial injury model; Ophiopogonin D; Oxidative stress; Inflammation; Apoptosis; AQUEOUS EXTRACT; 2; CONSTITUENTS; ACTIVATION; APOPTOSIS; DYSFUNCTION; MECHANISMS; JAPONICUS; PATHWAY; H2O2;
D O I
10.1016/j.jep.2010.01.031
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Aim of the study. Vessel endothelium injury caused by reactive oxygen species (ROS) including H2O2 plays a critical role in the pathogenesis of cardiovascular disorders Therefore, drug targeting ROS elimination has highly clinical values in cardiovascular therapy The plant of Radix Ophiopogon japonicus is a traditional Chinese herbal medicine that has been commonly used for prevention and treatment of cardiovascular diseases for a long history. However, the effective component mediating its beneficial effects remains unknown In the present study, we investigated the action of Ophiopogonin D (OP-D), one of the most bioactive components of Radix Ophiopogon japonicus, in an endothelial injury model induced by H2O2 Materials and methods. Primarily cultured human umbilical vein endothelial cells (HUVECs) were pre-treated with increased doses of OP-D overnight and then challenged with H2O2 The protective effects of OP-D against H2O2 were evaluated Results We found that OP-D inhibited mRNA levels of antioxidant, inflammatory and apoptotic genes in a dose-dependent manner in HUVECs H2O2-induced lipid peroxidation and protein carbonylation were reduced by OP-D pretreatment Mitochondria! ROS generation and cell apoptosis were also attenuated in OP-D pretreated cells In addition, OP-D restored cellular total antioxidative capacity and inhibited the release of inflammatory cytokines Furthermore, OP-D suppressed the enzymatic activity of catalase. HO-1, and caspases. Finally, OP-D blocked activation of NF-kappa B and ERK signaling cascades. Conclusion Our findings provide the first evidence that OP-D plays a protective role as an effective antioxidant in H2O2-induced endothelial injury Ophiopogonin D can be therefore developed as a novel drug for the therapy of cardiovascular disorders (C) 2010 Elsevier Ireland Ltd All rights reserved
引用
收藏
页码:438 / 445
页数:8
相关论文
共 27 条
[1]   Crosstalk via the NF-κB signaling system [J].
Basak, Soumen ;
Hoffmann, Alexander .
CYTOKINE & GROWTH FACTOR REVIEWS, 2008, 19 (3-4) :187-197
[2]   Mechanisms of caspase activation [J].
Boatright, KM ;
Salvesen, GS .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (06) :725-731
[3]   Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences [J].
Cai, H .
CARDIOVASCULAR RESEARCH, 2005, 68 (01) :26-36
[4]   Endothelial dysfunction in cardiovascular diseases - The role of oxidant stress [J].
Cai, H ;
Harrison, DG .
CIRCULATION RESEARCH, 2000, 87 (10) :840-844
[5]   H2O2 induces paracellular permeability of porcine brain-derived microvascular endothelial cells by activation of the p44/42 MAP kinase pathway [J].
Fischer, S ;
Wiesnet, M ;
Renz, D ;
Schaper, W .
EUROPEAN JOURNAL OF CELL BIOLOGY, 2005, 84 (07) :687-697
[6]   Mitochondria-Derived Reactive Oxygen Species Mediate Heme Oxygenase-1 Expression in Sheared Endothelial Cells [J].
Han, Zhaosheng ;
Varadharaj, Saradhadevi ;
Giedt, Randy J. ;
Zweier, Jay L. ;
Szeto, Hazel H. ;
Alevriadou, B. Rita .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2009, 329 (01) :94-101
[7]   RAPID SUPEROXIDE PRODUCTION BY ENDOTHELIAL-CELLS AND THEIR INJURY UPON REPERFUSION [J].
HASHIMOTO, Y ;
ITOH, K ;
NISHIDA, K ;
OKANO, T ;
MIYAZAWA, Y ;
OKINAGA, K .
JOURNAL OF SURGICAL RESEARCH, 1994, 57 (06) :693-697
[8]   Anti-inflammatory activities of aqueous extract from Radix ophiopogon japonicus and its two constituents [J].
Kou, JP ;
Sun, Y ;
Lin, YW ;
Cheng, ZH ;
Zheng, W ;
Yu, BY ;
Xu, Q .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2005, 28 (07) :1234-1238
[9]   Antithrombotic activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents [J].
Kou, Junping ;
Tian, Youqing ;
Tang, Yunkit ;
Yan, Jin ;
Yu, Boyang .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2006, 29 (06) :1267-1270
[10]   Caspase-9 [J].
Kuida, K .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2000, 32 (02) :121-124