Ophiopogonin D prevents H2O2-induced injury in primary human umbilical vein endothelial cells.
OBJECTIVE
Vessel endothelium injury caused by reactive oxygen species (ROS) including H(2)O(2) 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 H(2)O(2).


METHODS
Primarily cultured human umbilical vein endothelial cells (HUVECs) were pretreated with increased doses of OP-D overnight and then challenged with H(2)O(2). The protective effects of OP-D against H(2)O(2) were evaluated.


RESULTS
We found that OP-D inhibited mRNA levels of antioxidant, inflammatory and apoptotic genes in a dose-dependent manner in HUVECs. H(2)O(2)-induced lipid peroxidation and protein carbonylation were reduced by OP-D pretreatment. Mitochondrial 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-kappaB and ERK signaling cascades.


CONCLUSIONS
Our findings provide the first evidence that OP-D plays a protective role as an effective antioxidant in H(2)O(2)-induced endothelial injury. Ophiopogonin D can be therefore developed as a novel drug for the therapy of cardiovascular disorders.
Qian
Jinchun
J
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, #1 Wenyuan Rd, Nanjing, China.
Jiang
Fengrong
F
Wang
Bin
B
Yu
Yang
Y
Zhang
Xu
X
Yin
Zhimin
Z
Liu
Chang
C
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013150:Spirostans / Q000494:pharmacology*; D014471:Umbilical Veins / Q000378:metabolism*
D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012503:Saponins; D013150:Spirostans; C046996:ophiopogonin D; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D020169:Caspases