Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells.
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 proatherosclerotic stressor oxidized low-density lipoprotein (oxLDL) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5-100 microg/ml) for 2 h and then incubated with oxLDL (150 microg/ml) for an additional 24 h. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability, and several apoptotic indexes were assessed. Our data show 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 expression of endothelial NO synthase and enhanced expression of adhesion molecules (ICAM, VCAM, and E-selectin) 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.
Ou
Hsiu-Chung
HC
Division of Endocrinology and Metabolism, Dept. of Internal Medicine, Taichung Veterans General Hospital, No. 160, Sec. 3, Taichung-Kang Road, Taichung 407, Taiwan. whhsheu@vghtc.gov.tw
Lee
Wen-Jane
WJ
Lee
I-Te
IT
Chiu
Tsan-Hung
TH
Tsai
Kun-Ling
KL
Lin
Chih-Ying
CY
Sheu
Wayne Huey-Herng
WH
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology
D000975:Antioxidants; D008077:Lipoproteins, LDL; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase