title: Eugenosedin-A ameliorates hyperlipidemia-induced vascular endothelial dysfunction via inhibition of α1-adrenoceptor/5-HT activity and NADPH oxidase expression.
abstract: Eugenosedin-A (Eu-A) effects on vascular endothelial dysfunction and oxidative stress in a hyperlipidemic rat model were investigated. Rats were randomly divided into four groups: two control groups and two treatment groups. The control rats received a regular diet or high fat diet (HFD); the treatment rats fed received an HFD with 5 mg/kg Eu-A or atorvastatin for 10 weeks. No changes in serotonin levels were observed in the four groups; norepinephrine levels were enhanced in the HFD group which was attenuated by Eu-A and atorvastatin. In the HFD group, the vascular reactivity was increased by vasoconstrictors (5-nonyloxytryptamine, 5-HT, and phenylephrine) and decreased by an endothelium-dependent vasorelaxant, carbachol. Protein levels of α1-adrenergic receptors (not 5-HT1B/2A), reactive oxygen species (ROS) p47(phox), p67(phox), and gp91(phox), and oxidative damage markers 3-nitrotyrosine (3-NT) and 4-hydroxy-2-nonenal (4-HNE) were increased, but endothelial nitric oxide synthase (eNOS), P-eNOS and vasodilator-stimulated phosphoprotein phosphorylation (P-VASP) were decreased. Catalase and superoxide dismutase (SOD-1 and SOD-2) proteins were increased, but glutathione peroxidase (GPx) was decreased in the aorta. Eu-A and atorvastatin reduced vasoconstrictor-induced aortic contractions that might be related to 5-HT1B/2A and α1-adrenergic receptors inhibitory activities. Eu-A and atorvastatin improved eNOS/P-eNOS, P-VASP, GPx, and malondialdehyde (MDA) levels, and decreased ROS and oxidative damage markers. Taken together, we suggest that Eu-A can ameliorate hyperlipidemia-induced vascular endothelial dysfunction and oxidative dysregulation.
authors.affiliation: Department of Nursing, Meiho University, Pingtung, Taiwan.
authors.forename: Kuo-Ping
authors.initials: KP
authors.lastname: Shen
authors.affiliation: Department of Food Science and Nutrition, Meiho University, Pingtung, Taiwan.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Lin
authors.affiliation: Division of Hepatobiliarypancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Wen-Tsan
authors.initials: WT
authors.lastname: Chang
authors.affiliation: Department of Ophthalmology, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan.
authors.forename: Jou-Chun
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: An
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ing-Jun
authors.initials: IJ
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: binnan@kmu.edu.tw.
authors.forename: Bin-Nan
authors.initials: BN
authors.lastname: Wu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006949:Hyperlipidemias / Q000150:complications*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D017382:Reactive Oxygen Species; D011941:Receptors, Adrenergic; C496985:eugenosedin-A; D000098662:Vasodilator-Stimulated Phosphoprotein; D012701:Serotonin; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D009638:Norepinephrine
keywords: Atorvastatin; Endothelial dysfunction; Eugenosedin-A; Hyperlipidemia; Oxidative markers