title: Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells.
abstract: Aß40-induced vascular dysfunction has been implicated in the pathogenesis of Alzheimer׳s disease (AD). In the present study, we investigated the possible protective effects of puerarin against Aß40-induced vascular damage and impairment to angiogenesis in transgenic TG (fli1:EGFP) zebrafish and human endothelial cells. Aß40 peptides at 5μM caused an obvious reduction of vessel branches in the subintestinal vein basket, induced NADPH oxidase-derived reactive oxygen species and impaired vascular endothelial growth factor (VEGF)-dependent angiogenesis. Pretreatment with puerarin attenuated Aβ40-induced vessel reduction and impairment to angiogenesis in a dose-dependent manner. In addition, Aß40 decreased VEGF-dependent phosphorylation of Akt and eNOS, whereas puerarin treatment attenuated these detrimental effects. Furthermore, the restoration of Aß40-induced-angiogenesis impairment by puerarin was abolished by either the PI3 kinase inhibitor LY294002 (10μM) or eNOS inhibitor L-NAME. The present study suggests that puerarin exerts its protective action probably through reduction of NADPH oxidase-derived reactive oxygen species overproduction and activation of the PI3K/Akt/eNOS pathways.
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jun-Xiu
authors.initials: JX
authors.lastname: Liu
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Si-Mei
authors.initials: SM
authors.lastname: Long
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Min-Ying
authors.initials: MY
authors.lastname: Zheng
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Ren
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Wang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Su
authors.affiliation: Department of Medicine, The Faculty of Medicine, The University of Hong Kong, SAR, China.
authors.forename: Raymond Tak
authors.initials: RT
authors.lastname: Fai Cheung
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China. Electronic address: Huanxingsu@umac.mo.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: peizhong@mail.sysu.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D015027:Zebrafish
chemical_list: D016229:Amyloid beta-Peptides; D007529:Isoflavones; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C033607:puerarin
keywords: Aß40; Puerarin; Vascular protection; Zebrafish