Protective effects of magnolol against oxidized LDL-induced apoptosis in endothelial cells.
Magnolol, a compound extracted from the Chinese medicinal herb Magnolia officinalis, has several biological effects. However, its protective effects against endothelial injury remain unclear. In this study, we examined whether magnolol prevents oxidized low density lipoprotein (oxLDL)-induced vascular endothelial apoptosis. Incubation of oxLDL with magnolol (2.5-20 microM) inhibited copper-induced oxidative modification via diene formation, thiobarbituric acid reactive substances (TBARS) assay and electrophoretic mobility assay. Apoptotic cell death as characterized by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stain. We measured the production of reactive oxygen species (ROS) by using the fluorescent probe 2',7'-dichlorofluorescein acetoxymethyl ester (DCF-AM), and observed the activity of antioxidant enzymes. Furthermore, several apoptotic signaling pathways which showed NF-kappaB activation, increased cytosolic calcium, alteration of mitochondrial membrane potential, cytochrome c release and activation of caspase 3 were also investigated. We demonstrated that magnolol prevented the copper-induced oxidative modification of LDL. Magnolol attenuated the oxLDL-induced ROS generation and subsequent NF-kappaB activation. Furthermore, intracellular calcium accumulation and subsequent mitochondrial membrane potential collapse, cytochome c release and activation of caspase 3 caused by oxLDL were also inhibited by magnolol. Our results suggest that magnolol may have clinical implications in the prevention of atherosclerotic vascular disease through decreasing the oxLDL-induced ROS production.
Ou
Hsiu-Chung
HC
Department of Education and Medical Research, Taichung Veterans General Hospital, No. 160, Sec. 3, Taichung-Kang Road, Taichung, 407, Taiwan.
Chou
Fen-Pi
FP
Sheu
Wayne Huey-Herng
WH
Hsu
Shih-Lan
SL
Lee
Wen-Jane
WJ
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019327:Copper Sulfate / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D001713:Biphenyl Compounds; D017705:Lignans; D008077:Lipoproteins, LDL; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; C005498:magnolol; D045304:Cytochromes c; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D019327:Copper Sulfate; D002118:Calcium