Submitted on October 24, 2008
Revised on February 17, 2009
Accepted on February 18, 2009
Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells
Hsiu-Chung Ou1, Wen-Jane Lee2, I-Te Lee2, Tsan-Hung Chiu3, Kun-Ling Tsai4, Chih-Ying Lin5, and Wayne Huey-Herng Sheu6*
1 Graduate institute of Rebabilitation Science,
2 Taichung Veterans General Hospital
3 China Medical University Hospital
4 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
5 China Medical University
6 Division of Endo. & Metab., Veteran's General Hosp. Taichung Taiwan
* To whom correspondence should be addressed. E-mail: whhsheu{at}vghtc.gov.tw.
Atherosclerosis is a chronic inflammatory process with increased oxidative stress in vascular endothelium. Ginkgo biloba extract (GbE), extracted from Ginkgo biloba leaves, has commonly been used as a therapeutic agent for cardiovascular and neurological disorders. The aim of this study was to investigate how GbE protects vascular endothelial cells against the pro-atherosclerotic stressor, oxidized low-density lipoprotein (oxLDL), in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5-100 µg/ml) for 2 hours and then were incubated with oxLDL (150 µg/ml) for an additional 24 hours. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability and several apoptotic indexes were assessed. Our data showed that ROS generation is an upstream signal in oxLDL-treated HUVECs. Cu, Zn-SOD, but not Mn-SOD, was inactivated by oxLDL. In addition, oxLDL diminished endothelial NO synthase (eNOS) expression, enhanced adhesion molecules (ICAM, VCAM and E-selectin) expression, and the adherence of monocytic THP-1 cells to HUVECs. Furthermore, oxLDL increased intracellular calcium, disturbed the balance of Bcl-2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose-dependently by GbE (p<0.05). Results from this study may provide insight into a possible molecular mechanism underlying GbE suppression of the oxLDL-mediated vascular endothelial dysfunction.
