Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach
Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti...
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| creator | Yao, Benxing Xu, Di Wang, Qing Liu, Lin Hu, Ziyun Liu, Wenya Zheng, Qi Meng, Huihui Xiao, Ran Xu, Qian Hu, Yudie Wang, Junsong |
| description | Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD. |
| doi_str_mv | 10.1007/s11011-024-01387-8 |
| format | Article |
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Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD.</description><identifier>ISSN: 1573-7365</identifier><identifier>ISSN: 0885-7490</identifier><identifier>EISSN: 1573-7365</identifier><identifier>DOI: 10.1007/s11011-024-01387-8</identifier><identifier>PMID: 39002017</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Amino acids ; Angiogenesis ; Animals ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Blood circulation ; Blood vessels ; Cell proliferation ; Cell size ; Cell survival ; Chromatography, Liquid ; Damage ; Drugs, Chinese Herbal - pharmacology ; Drugs, Chinese Herbal - therapeutic use ; Endothelial cells ; Energy metabolism ; Herbal medicine ; Herbs ; Histopathology ; Ischemia ; Ischemic Stroke - drug therapy ; Ischemic Stroke - metabolism ; Liquid Chromatography-Mass Spectrometry ; Male ; Metabolic Diseases ; Metabolism ; Metabolites ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Neurology ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Neurosciences ; Oncology ; Oxidative metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Stroke ; Tandem Mass Spectrometry ; Thromboembolism ; Thrombosis ; Traditional Chinese medicine ; Tricarboxylic acid cycle</subject><ispartof>Metabolic brain disease, 2024-08, Vol.39 (6), p.1131-1148</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. 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Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. 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This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD.</description><subject>Amino acids</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood circulation</subject><subject>Blood vessels</subject><subject>Cell proliferation</subject><subject>Cell size</subject><subject>Cell survival</subject><subject>Chromatography, Liquid</subject><subject>Damage</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Drugs, Chinese Herbal - therapeutic use</subject><subject>Endothelial cells</subject><subject>Energy metabolism</subject><subject>Herbal medicine</subject><subject>Herbs</subject><subject>Histopathology</subject><subject>Ischemia</subject><subject>Ischemic Stroke - drug therapy</subject><subject>Ischemic Stroke - metabolism</subject><subject>Liquid Chromatography-Mass Spectrometry</subject><subject>Male</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neurology</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neurosciences</subject><subject>Oncology</subject><subject>Oxidative metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Stroke</subject><subject>Tandem Mass Spectrometry</subject><subject>Thromboembolism</subject><subject>Thrombosis</subject><subject>Traditional Chinese medicine</subject><subject>Tricarboxylic acid cycle</subject><issn>1573-7365</issn><issn>0885-7490</issn><issn>1573-7365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kb9uFDEQxi1ERELgBSiQJRoaE3u9tndLdCEB6QJFoKGx_Gd853C7vti7J-Up8spxuEAiCiqPZ37zfSN9CL1h9AOjVJ0UxihjhDYtoYx3inTP0BETihPFpXj-pD5EL0u5opRywfoX6JD3lDaUqSN0-xXmnLY5TeCmuANsRo93pjxtQQi1KjgFvIZs8dbEfP_5uY7X0SRyasbVao44jjgWt4YhOlymnH4BnkeXdpDBY3uDlwtycXlycUmsKbUzwGRs2qSKF2y21dC49St0EMymwOuH9xj9OPv0ffGZLL-df1l8XBLXCDkRJjw4kF41TDjBgDofbFACWNtJpaTntu19p7oQmA22FQG48Ao4lz4A9PwYvd_rVtvrGcqkh3o7bDZmhDQXzanqeyE7Riv67h_0Ks15rNdVqleSStGqSjV7yuVUSoagtzkOJt9oRvV9XHofl65x6d9x6a4uvX2Qnu0A_u_Kn3wqwPdAqaNxBfnR-z-yd5htonw</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Yao, Benxing</creator><creator>Xu, Di</creator><creator>Wang, Qing</creator><creator>Liu, Lin</creator><creator>Hu, Ziyun</creator><creator>Liu, Wenya</creator><creator>Zheng, Qi</creator><creator>Meng, Huihui</creator><creator>Xiao, Ran</creator><creator>Xu, Qian</creator><creator>Hu, Yudie</creator><creator>Wang, Junsong</creator><general>Springer US</general><general>Springer Nature 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>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20240801</creationdate><title>Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach</title><author>Yao, Benxing ; Xu, Di ; Wang, Qing ; Liu, Lin ; Hu, Ziyun ; Liu, Wenya ; Zheng, Qi ; Meng, Huihui ; Xiao, Ran ; Xu, Qian ; Hu, Yudie ; Wang, Junsong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c256t-15dece6d7215c51e0cdfbf75e1486776d3b49d878ff1bfb45fe35d7e336dfee93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amino acids</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood circulation</topic><topic>Blood vessels</topic><topic>Cell proliferation</topic><topic>Cell size</topic><topic>Cell survival</topic><topic>Chromatography, Liquid</topic><topic>Damage</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Drugs, Chinese Herbal - therapeutic use</topic><topic>Endothelial cells</topic><topic>Energy metabolism</topic><topic>Herbal medicine</topic><topic>Herbs</topic><topic>Histopathology</topic><topic>Ischemia</topic><topic>Ischemic Stroke - drug therapy</topic><topic>Ischemic Stroke - metabolism</topic><topic>Liquid Chromatography-Mass Spectrometry</topic><topic>Male</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neurology</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Neurosciences</topic><topic>Oncology</topic><topic>Oxidative metabolism</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Stroke</topic><topic>Tandem Mass Spectrometry</topic><topic>Thromboembolism</topic><topic>Thrombosis</topic><topic>Traditional Chinese medicine</topic><topic>Tricarboxylic acid cycle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yao, Benxing</creatorcontrib><creatorcontrib>Xu, Di</creatorcontrib><creatorcontrib>Wang, Qing</creatorcontrib><creatorcontrib>Liu, Lin</creatorcontrib><creatorcontrib>Hu, Ziyun</creatorcontrib><creatorcontrib>Liu, Wenya</creatorcontrib><creatorcontrib>Zheng, Qi</creatorcontrib><creatorcontrib>Meng, Huihui</creatorcontrib><creatorcontrib>Xiao, Ran</creatorcontrib><creatorcontrib>Xu, Qian</creatorcontrib><creatorcontrib>Hu, Yudie</creatorcontrib><creatorcontrib>Wang, Junsong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Metabolic brain disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yao, Benxing</au><au>Xu, Di</au><au>Wang, Qing</au><au>Liu, Lin</au><au>Hu, Ziyun</au><au>Liu, Wenya</au><au>Zheng, Qi</au><au>Meng, Huihui</au><au>Xiao, Ran</au><au>Xu, Qian</au><au>Hu, Yudie</au><au>Wang, Junsong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach</atitle><jtitle>Metabolic brain disease</jtitle><stitle>Metab Brain Dis</stitle><addtitle>Metab Brain Dis</addtitle><date>2024-08-01</date><risdate>2024</risdate><volume>39</volume><issue>6</issue><spage>1131</spage><epage>1148</epage><pages>1131-1148</pages><issn>1573-7365</issn><issn>0885-7490</issn><eissn>1573-7365</eissn><abstract>Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>39002017</pmid><doi>10.1007/s11011-024-01387-8</doi><tpages>18</tpages></addata></record> |
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| subjects | Amino acids Angiogenesis Animals Apoptosis Biochemistry Biomedical and Life Sciences Biomedicine Blood circulation Blood vessels Cell proliferation Cell size Cell survival Chromatography, Liquid Damage Drugs, Chinese Herbal - pharmacology Drugs, Chinese Herbal - therapeutic use Endothelial cells Energy metabolism Herbal medicine Herbs Histopathology Ischemia Ischemic Stroke - drug therapy Ischemic Stroke - metabolism Liquid Chromatography-Mass Spectrometry Male Metabolic Diseases Metabolism Metabolites Metabolomics Mice Mice, Inbred C57BL Neurology Neuroprotection Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Neurosciences Oncology Oxidative metabolism Oxidative stress Oxidative Stress - drug effects Stroke Tandem Mass Spectrometry Thromboembolism Thrombosis Traditional Chinese medicine Tricarboxylic acid cycle |
| title | Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach |
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