Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells
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 huma...
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| Veröffentlicht in: | European journal of pharmacology 2014-06, Vol.732, p.76-85 |
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| creator | Lu, Xi-Lin Liu, Jun-Xiu Wu, Qi Long, Si-Mei Zheng, Min-Ying Yao, Xiao-Li Ren, Huixia Wang, Yong-Gang Su, Wei-Wei Fai Cheung, Raymond Tak Zeng, Jin-Sheng Su, Huanxing Pei, Zhong |
| description | 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. |
| doi_str_mv | 10.1016/j.ejphar.2014.03.030 |
| format | Article |
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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.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2014.03.030</identifier><identifier>PMID: 24690262</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Amyloid beta-Peptides - antagonists & inhibitors ; Amyloid beta-Peptides - toxicity ; Animals ; Aß40 ; Endothelial Cells - drug effects ; Humans ; Isoflavones - pharmacology ; Neovascularization, Physiologic - drug effects ; Neuroprotective Agents - pharmacology ; Puerarin ; Reactive Oxygen Species - metabolism ; Respiratory Burst - drug effects ; Vascular Diseases - chemically induced ; Vascular Diseases - pathology ; Vascular Diseases - prevention & control ; Vascular protection ; Zebrafish</subject><ispartof>European journal of pharmacology, 2014-06, Vol.732, p.76-85</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c277t-1f4886de136917202b517a3bb91a7c684b6161670d318ee2dc6e048766878093</citedby><cites>FETCH-LOGICAL-c277t-1f4886de136917202b517a3bb91a7c684b6161670d318ee2dc6e048766878093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2014.03.030$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24690262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Xi-Lin</creatorcontrib><creatorcontrib>Liu, Jun-Xiu</creatorcontrib><creatorcontrib>Wu, Qi</creatorcontrib><creatorcontrib>Long, Si-Mei</creatorcontrib><creatorcontrib>Zheng, Min-Ying</creatorcontrib><creatorcontrib>Yao, Xiao-Li</creatorcontrib><creatorcontrib>Ren, Huixia</creatorcontrib><creatorcontrib>Wang, Yong-Gang</creatorcontrib><creatorcontrib>Su, Wei-Wei</creatorcontrib><creatorcontrib>Fai Cheung, Raymond Tak</creatorcontrib><creatorcontrib>Zeng, Jin-Sheng</creatorcontrib><creatorcontrib>Su, Huanxing</creatorcontrib><creatorcontrib>Pei, Zhong</creatorcontrib><title>Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>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.</description><subject>Amyloid beta-Peptides - antagonists & inhibitors</subject><subject>Amyloid beta-Peptides - toxicity</subject><subject>Animals</subject><subject>Aß40</subject><subject>Endothelial Cells - drug effects</subject><subject>Humans</subject><subject>Isoflavones - pharmacology</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Puerarin</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Respiratory Burst - drug effects</subject><subject>Vascular Diseases - chemically induced</subject><subject>Vascular Diseases - pathology</subject><subject>Vascular Diseases - prevention & control</subject><subject>Vascular protection</subject><subject>Zebrafish</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM9qGzEQh0VpiN0kb1CKjr2sM9Ku9edSMKFJC4bk4LvQSrO1zFrrSruG9GXyMHmxyjjtMWhAAn2_Gekj5DODBQMmbncL3B22Ni04sGYBdSn4QOZMSV2BZPwjmUO5qbjWekY-5bwDgKXmy0sy443QwAWfk_SUhhHdGI5IsevKKdOho4cJk00hUvvLhphHunp9aaAK0U8OPT3a7KbeJuqfczfFEh8iLfQfbJPtQt5SGz3dTnsbKUY_jFvsg-2pw77P1-Sis33Gm7f9imzuv2_uflTrx4efd6t15biUY8W6RinhkdVCM8mBt0smbd22mlnphGpawcqS4GumELl3AqFRUgglFej6inw9tz2k4feEeTT7kE8PsBGHKRu25KyuiyhV0OaMujTknLAzhxT2Nj0bBuYk2-zMWbY5yTZQl4IS-_I2YWr36P-H_tktwLczgOWbx4DJZBcwFoMhFdPGD-H9CX8Bc12S-w</recordid><startdate>20140605</startdate><enddate>20140605</enddate><creator>Lu, Xi-Lin</creator><creator>Liu, Jun-Xiu</creator><creator>Wu, Qi</creator><creator>Long, Si-Mei</creator><creator>Zheng, Min-Ying</creator><creator>Yao, Xiao-Li</creator><creator>Ren, Huixia</creator><creator>Wang, Yong-Gang</creator><creator>Su, Wei-Wei</creator><creator>Fai Cheung, Raymond Tak</creator><creator>Zeng, Jin-Sheng</creator><creator>Su, Huanxing</creator><creator>Pei, Zhong</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140605</creationdate><title>Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells</title><author>Lu, Xi-Lin ; Liu, Jun-Xiu ; Wu, Qi ; Long, Si-Mei ; Zheng, Min-Ying ; Yao, Xiao-Li ; Ren, Huixia ; Wang, Yong-Gang ; Su, Wei-Wei ; Fai Cheung, Raymond Tak ; Zeng, Jin-Sheng ; Su, Huanxing ; Pei, Zhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c277t-1f4886de136917202b517a3bb91a7c684b6161670d318ee2dc6e048766878093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amyloid beta-Peptides - antagonists & inhibitors</topic><topic>Amyloid beta-Peptides - toxicity</topic><topic>Animals</topic><topic>Aß40</topic><topic>Endothelial Cells - drug effects</topic><topic>Humans</topic><topic>Isoflavones - pharmacology</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Puerarin</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Respiratory Burst - drug effects</topic><topic>Vascular Diseases - chemically induced</topic><topic>Vascular Diseases - pathology</topic><topic>Vascular Diseases - prevention & control</topic><topic>Vascular protection</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Xi-Lin</creatorcontrib><creatorcontrib>Liu, Jun-Xiu</creatorcontrib><creatorcontrib>Wu, Qi</creatorcontrib><creatorcontrib>Long, Si-Mei</creatorcontrib><creatorcontrib>Zheng, Min-Ying</creatorcontrib><creatorcontrib>Yao, Xiao-Li</creatorcontrib><creatorcontrib>Ren, Huixia</creatorcontrib><creatorcontrib>Wang, Yong-Gang</creatorcontrib><creatorcontrib>Su, Wei-Wei</creatorcontrib><creatorcontrib>Fai Cheung, Raymond Tak</creatorcontrib><creatorcontrib>Zeng, Jin-Sheng</creatorcontrib><creatorcontrib>Su, Huanxing</creatorcontrib><creatorcontrib>Pei, Zhong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Xi-Lin</au><au>Liu, Jun-Xiu</au><au>Wu, Qi</au><au>Long, Si-Mei</au><au>Zheng, Min-Ying</au><au>Yao, Xiao-Li</au><au>Ren, Huixia</au><au>Wang, Yong-Gang</au><au>Su, Wei-Wei</au><au>Fai Cheung, Raymond Tak</au><au>Zeng, Jin-Sheng</au><au>Su, Huanxing</au><au>Pei, Zhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2014-06-05</date><risdate>2014</risdate><volume>732</volume><spage>76</spage><epage>85</epage><pages>76-85</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24690262</pmid><doi>10.1016/j.ejphar.2014.03.030</doi><tpages>10</tpages></addata></record> |
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| subjects | Amyloid beta-Peptides - antagonists & inhibitors Amyloid beta-Peptides - toxicity Animals Aß40 Endothelial Cells - drug effects Humans Isoflavones - pharmacology Neovascularization, Physiologic - drug effects Neuroprotective Agents - pharmacology Puerarin Reactive Oxygen Species - metabolism Respiratory Burst - drug effects Vascular Diseases - chemically induced Vascular Diseases - pathology Vascular Diseases - prevention & control Vascular protection Zebrafish |
| title | Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells |
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