Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 128, Issue 2, Pages 438-445Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2010.01.031
Keywords
Endothelial injury model; Ophiopogonin D; Oxidative stress; Inflammation; Apoptosis
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Funding
- Chinese National Science Foundation [30870928]
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [09KJA180003]
- Nanjing Normal University Outstanding Talents Program [2008104XGQ0065]
- Opening Project of Jiangsu Key Laboratory for Molecular and Medical Biotechnology [MMBO9KF05]
- Mega-projects of Science Research for the 11th Five-year Plan of China [2009ZX09302]
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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
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