title: Ginkgo biloba extract attenuates oxLDL-induced endothelial dysfunction via an AMPK-dependent mechanism.
abstract: Atherosclerosis is a complex inflammatory arterial disease, and oxidized low-density lipoprotein (oxLDL) is directly associated with chronic vascular inflammation. Previous studies have shown that Ginkgo biloba extract (GbE) acts as a therapeutic agent for neurological and cardiovascular disorders. However, the mechanisms mediating the actions of GbE are still largely unknown. In the present study, we tested the hypothesis that GbE protects against oxLDL-induced endothelial dysfunction via an AMP-activated protein kinase (AMPK)-dependent mechanism. Human umbilical vein endothelial cells were treated with GbE, followed by oxLDL, for indicated time periods. Results from Western blot showed that GbE inhibited the membrane translocation of the NADPH oxidase subunits p47(phox) and Rac-1 and attenuated the increase in protein expression of membrane subunits gp91 and p22(phox) caused by oxLDL-induced AMPK dephosphorylation and subsequent PKC activation. AMPK-α(1)-specific small interfering RNA-transfected cells that had been exposed to GbE followed by oxLDL revealed elevated levels of PKC and p47(phox). In addition, exposure to oxLDL resulted in reduced AMPK-mediated Akt/endothelial nitric oxide (NO) synthase signaling and the induction of phosphorylation of p38 mitogen-activated protein kinase, which, in turn, activated NF-κB-mediated inflammatory responses, such as the release of interleukin-8, the expression of the adhesion molecule, and the adherence of monocytic cells to human umbilical vein endothelial cells. Furthermore, oxLDL upregulated the expression of inducible NO synthase, thereby augmenting the formation of NO and protein nitrosylation. Pretreatment with GbE, however, exerted significant cytoprotective effects in a dose-dependent manner. Results from this study may provide insight into a possible molecular mechanism by which GbE protects against oxLDL-induced endothelial dysfunction.
authors.affiliation: Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
authors.forename: Hsiu-Chung
authors.initials: HC
authors.lastname: Ou
authors.forename: Yueh-Ling
authors.initials: YL
authors.lastname: Hsieh
authors.forename: Nae-Cherng
authors.initials: NC
authors.lastname: Yang
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Tsai
authors.forename: Kai-Ling
authors.initials: KL
authors.lastname: Chen
authors.forename: Chiou-Sheng
authors.initials: CS
authors.lastname: Tsai
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Chen
authors.forename: Bor-Tsang
authors.initials: BT
authors.lastname: Wu
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D020441:Ginkgo biloba; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C086986:CYBA protein, human; C060505:neutrophil cytosolic factor 1; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases