Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke in rats via inhibition of HIF-1 α, VEGF and promotion β-ENaC expression

Bu Yang Huan Wu Decoction (BYHW) is a famous traditional Chinese medicine (TCM) formula used in China for the treatment of cerebral ischemic stroke. But the protective effects and underlining mechanisms of BYHW remain unclear. This study was designed to investigate the protective effects and underli...

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Veröffentlicht in:Journal of ethnopharmacology 2019-01, Vol.228, p.70-81
Hauptverfasser: Chen, Zhen-Zhen, Gong, Xin, Guo, Qi, Zhao, Hui, Wang, Lei
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Gong, Xin
Guo, Qi
Zhao, Hui
Wang, Lei
description Bu Yang Huan Wu Decoction (BYHW) is a famous traditional Chinese medicine (TCM) formula used in China for the treatment of cerebral ischemic stroke. But the protective effects and underlining mechanisms of BYHW remain unclear. This study was designed to investigate the protective effects and underlining signaling mechanisms of BYHW on brain tissues in a rat model of cerebral ischemic reperfusion (I/R) injury. Liquid chromatography was used to verify the composition of BYHW. The cerebral edema and infarct volume were measured by magnetic resonance imaging (MRI). The morphology and ultrastructure of ischemic penumbra brain tissues were observed by hematoxylin-eosin (HE) and transmission electron microscopy (TEM). The expression levels of HIF-1 α, VEGF and β-ENaC were tested using immunohistochemistry technique, western blot and quantitative PCR analysis, respectively. Administration of BYHW significantly decreased cerebral edema, rat neurological function scores, reduced brain infarct volume. At the same time, BYHW had protective effect on the blood-brain barrier (BBB), which improved the morphology and ultrastructure of ischemic penumbra brain tissues. BYHW treatment significantly decreased the protein and mRNA levels of HIF-1 α and VEGF compared with the model treatment. In addition, BYHW treatment significantly up-regulated the protein and mRNA levels of β-ENaC. BYHW protected against cerebral I/R injury in MCAO rats through inhibiting the activation of the HIF-1 α /VEGF pathway and stabilizing ion channel of β-ENaC in brain, indicating that BYHW shows potential for stroke treatment in acute stage. [Display omitted]
doi_str_mv 10.1016/j.jep.2018.09.017
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But the protective effects and underlining mechanisms of BYHW remain unclear. This study was designed to investigate the protective effects and underlining signaling mechanisms of BYHW on brain tissues in a rat model of cerebral ischemic reperfusion (I/R) injury. Liquid chromatography was used to verify the composition of BYHW. The cerebral edema and infarct volume were measured by magnetic resonance imaging (MRI). The morphology and ultrastructure of ischemic penumbra brain tissues were observed by hematoxylin-eosin (HE) and transmission electron microscopy (TEM). The expression levels of HIF-1 α, VEGF and β-ENaC were tested using immunohistochemistry technique, western blot and quantitative PCR analysis, respectively. Administration of BYHW significantly decreased cerebral edema, rat neurological function scores, reduced brain infarct volume. At the same time, BYHW had protective effect on the blood-brain barrier (BBB), which improved the morphology and ultrastructure of ischemic penumbra brain tissues. BYHW treatment significantly decreased the protein and mRNA levels of HIF-1 α and VEGF compared with the model treatment. In addition, BYHW treatment significantly up-regulated the protein and mRNA levels of β-ENaC. BYHW protected against cerebral I/R injury in MCAO rats through inhibiting the activation of the HIF-1 α /VEGF pathway and stabilizing ion channel of β-ENaC in brain, indicating that BYHW shows potential for stroke treatment in acute stage. [Display omitted]</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2018.09.017</identifier><identifier>PMID: 30218809</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; BBB ; Cerebral edema ; Cerebral ischemia reperfusion ; Drugs, Chinese Herbal - pharmacology ; Drugs, Chinese Herbal - therapeutic use ; Epithelial Sodium Channels - metabolism ; HIF-1 α ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Infarction, Middle Cerebral Artery - drug therapy ; Infarction, Middle Cerebral Artery - metabolism ; Infarction, Middle Cerebral Artery - pathology ; Male ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Rats, Sprague-Dawley ; Reperfusion Injury - drug therapy ; Reperfusion Injury - metabolism ; Reperfusion Injury - pathology ; Stroke - drug therapy ; Stroke - metabolism ; Stroke - pathology ; Vascular Endothelial Growth Factor A - metabolism ; VEGF ; β-ENaC</subject><ispartof>Journal of ethnopharmacology, 2019-01, Vol.228, p.70-81</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. 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But the protective effects and underlining mechanisms of BYHW remain unclear. This study was designed to investigate the protective effects and underlining signaling mechanisms of BYHW on brain tissues in a rat model of cerebral ischemic reperfusion (I/R) injury. Liquid chromatography was used to verify the composition of BYHW. The cerebral edema and infarct volume were measured by magnetic resonance imaging (MRI). The morphology and ultrastructure of ischemic penumbra brain tissues were observed by hematoxylin-eosin (HE) and transmission electron microscopy (TEM). The expression levels of HIF-1 α, VEGF and β-ENaC were tested using immunohistochemistry technique, western blot and quantitative PCR analysis, respectively. Administration of BYHW significantly decreased cerebral edema, rat neurological function scores, reduced brain infarct volume. At the same time, BYHW had protective effect on the blood-brain barrier (BBB), which improved the morphology and ultrastructure of ischemic penumbra brain tissues. BYHW treatment significantly decreased the protein and mRNA levels of HIF-1 α and VEGF compared with the model treatment. In addition, BYHW treatment significantly up-regulated the protein and mRNA levels of β-ENaC. BYHW protected against cerebral I/R injury in MCAO rats through inhibiting the activation of the HIF-1 α /VEGF pathway and stabilizing ion channel of β-ENaC in brain, indicating that BYHW shows potential for stroke treatment in acute stage. [Display omitted]</description><subject>Animals</subject><subject>BBB</subject><subject>Cerebral edema</subject><subject>Cerebral ischemia reperfusion</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Drugs, Chinese Herbal - therapeutic use</subject><subject>Epithelial Sodium Channels - metabolism</subject><subject>HIF-1 α</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Infarction, Middle Cerebral Artery - drug therapy</subject><subject>Infarction, Middle Cerebral Artery - metabolism</subject><subject>Infarction, Middle Cerebral Artery - pathology</subject><subject>Male</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Rats, Sprague-Dawley</subject><subject>Reperfusion Injury - drug therapy</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - pathology</subject><subject>Stroke - drug therapy</subject><subject>Stroke - metabolism</subject><subject>Stroke - pathology</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF</subject><subject>β-ENaC</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EokPhAdggL1mQcG-cTByxgtFMp1IFG37EynKcG-qQiQc7Geij9DHKg_SZcDqFJStb9nfO8fVh7DlCioDL113a0T7NAGUKVQpYPmALlGWWlEUpHrIFiFImsszxhD0JoQOAEnN4zE4EZCglVAt2_W7iX_XwjW8nPfAvE2_IODNaN_C9pwMNY-Ce9uTbKcyHdugmf8Vb1_fup406G8wl7azhYfTuO0WAex1FB6vj_tLW9s7MtXx7vkmQ39684p_XZxuuhyZGuJ27u7_9nazf6xWnXzE2zFFP2aNW94Ge3a-n7NNm_XG1TS4-nJ2v3l4kRhRiTHKJCBW0VOOyJlNhnBKyZY5QUl2JVlOrhSaQgqpM1FnEBCwrKWvC-DOFOGUvj77xMT8mCqPaxZmo7_VAbgoqQyggx7yYUTyixrsQPLVq7-1O-yuFoOZGVKdiI2puREGlYiNR8-Lefqp31PxT_K0gAm-OAMUhD5a8CsbSYKixnsyoGmf_Y_8HmfWdng</recordid><startdate>20190110</startdate><enddate>20190110</enddate><creator>Chen, Zhen-Zhen</creator><creator>Gong, Xin</creator><creator>Guo, Qi</creator><creator>Zhao, Hui</creator><creator>Wang, Lei</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>20190110</creationdate><title>Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke in rats via inhibition of HIF-1 α, VEGF and promotion β-ENaC expression</title><author>Chen, Zhen-Zhen ; Gong, Xin ; Guo, Qi ; Zhao, Hui ; Wang, Lei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-4811090feb16bec910000264107eb93faefa3ae083e923b2b16306988be174153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>BBB</topic><topic>Cerebral edema</topic><topic>Cerebral ischemia reperfusion</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Drugs, Chinese Herbal - therapeutic use</topic><topic>Epithelial Sodium Channels - metabolism</topic><topic>HIF-1 α</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Infarction, Middle Cerebral Artery - drug therapy</topic><topic>Infarction, Middle Cerebral Artery - metabolism</topic><topic>Infarction, Middle Cerebral Artery - pathology</topic><topic>Male</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Rats, Sprague-Dawley</topic><topic>Reperfusion Injury - drug therapy</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - pathology</topic><topic>Stroke - drug therapy</topic><topic>Stroke - metabolism</topic><topic>Stroke - pathology</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF</topic><topic>β-ENaC</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Zhen-Zhen</creatorcontrib><creatorcontrib>Gong, Xin</creatorcontrib><creatorcontrib>Guo, Qi</creatorcontrib><creatorcontrib>Zhao, Hui</creatorcontrib><creatorcontrib>Wang, Lei</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>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Zhen-Zhen</au><au>Gong, Xin</au><au>Guo, Qi</au><au>Zhao, Hui</au><au>Wang, Lei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke in rats via inhibition of HIF-1 α, VEGF and promotion β-ENaC expression</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2019-01-10</date><risdate>2019</risdate><volume>228</volume><spage>70</spage><epage>81</epage><pages>70-81</pages><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>Bu Yang Huan Wu Decoction (BYHW) is a famous traditional Chinese medicine (TCM) formula used in China for the treatment of cerebral ischemic stroke. But the protective effects and underlining mechanisms of BYHW remain unclear. This study was designed to investigate the protective effects and underlining signaling mechanisms of BYHW on brain tissues in a rat model of cerebral ischemic reperfusion (I/R) injury. Liquid chromatography was used to verify the composition of BYHW. The cerebral edema and infarct volume were measured by magnetic resonance imaging (MRI). The morphology and ultrastructure of ischemic penumbra brain tissues were observed by hematoxylin-eosin (HE) and transmission electron microscopy (TEM). The expression levels of HIF-1 α, VEGF and β-ENaC were tested using immunohistochemistry technique, western blot and quantitative PCR analysis, respectively. Administration of BYHW significantly decreased cerebral edema, rat neurological function scores, reduced brain infarct volume. At the same time, BYHW had protective effect on the blood-brain barrier (BBB), which improved the morphology and ultrastructure of ischemic penumbra brain tissues. BYHW treatment significantly decreased the protein and mRNA levels of HIF-1 α and VEGF compared with the model treatment. In addition, BYHW treatment significantly up-regulated the protein and mRNA levels of β-ENaC. BYHW protected against cerebral I/R injury in MCAO rats through inhibiting the activation of the HIF-1 α /VEGF pathway and stabilizing ion channel of β-ENaC in brain, indicating that BYHW shows potential for stroke treatment in acute stage. [Display omitted]</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>30218809</pmid><doi>10.1016/j.jep.2018.09.017</doi><tpages>12</tpages></addata></record>
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subjects Animals
BBB
Cerebral edema
Cerebral ischemia reperfusion
Drugs, Chinese Herbal - pharmacology
Drugs, Chinese Herbal - therapeutic use
Epithelial Sodium Channels - metabolism
HIF-1 α
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Infarction, Middle Cerebral Artery - drug therapy
Infarction, Middle Cerebral Artery - metabolism
Infarction, Middle Cerebral Artery - pathology
Male
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
Rats, Sprague-Dawley
Reperfusion Injury - drug therapy
Reperfusion Injury - metabolism
Reperfusion Injury - pathology
Stroke - drug therapy
Stroke - metabolism
Stroke - pathology
Vascular Endothelial Growth Factor A - metabolism
VEGF
β-ENaC
title Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke in rats via inhibition of HIF-1 α, VEGF and promotion β-ENaC expression
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