Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway
Receptor-interacting protein kinase 1/3 (RIPK1/3) and mixed lineage kinase domain-like (MLKL)-mediated necroptosis contributes to brain injury after ischemic stroke. Ligustroflavone is an ingredient of common privet with activities of anti-inflammation and complement inhibition. This study aims to e...
Gespeichert in:
| Veröffentlicht in: | Naunyn-Schmiedeberg's archives of pharmacology 2019-09, Vol.392 (9), p.1085-1095 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1095 |
|---|---|
| container_issue | 9 |
| container_start_page | 1085 |
| container_title | Naunyn-Schmiedeberg's archives of pharmacology |
| container_volume | 392 |
| creator | Zhang, Yi-Yue Liu, Wei-Ning Li, Yue-Qi Zhang, Xiao-Jie Yang, Jie Luo, Xiu-Ju Peng, Jun |
| description | Receptor-interacting protein kinase 1/3 (RIPK1/3) and mixed lineage kinase domain-like (MLKL)-mediated necroptosis contributes to brain injury after ischemic stroke. Ligustroflavone is an ingredient of
common privet
with activities of anti-inflammation and complement inhibition. This study aims to explore the effect of ligustroflavone on ischemic brain injury in stroke rat and the underlying mechanisms. A rat model of ischemic stroke was established by middle cerebral artery occlusion (MCAO), which showed ischemic injury (increase in neurological deficit score and infarct volume) and upregulation of necroptosis-associated proteins (RIPK1, RIPK3 and MLKL/p-MLKL). Administration of ligustroflavone (30 mg/kg, i.g.) 15 min before ischemia evidently improved neurological function, reduced infarct volume, and decreased the levels of necroptosis-associated proteins except the RIPK1. Consistently, hypoxia-cultured PC12 cells (O
2
/N2/CO
2
, 1:94:5, 8 h) caused cellular injury (LDH release and necroposis) concomitant with up-regulation of necroptosis-associated proteins, and these phenomena were blocked in the presence of ligustroflavone (25 μM) except the elevated RIPK1 levels. Using the Molecular Operating Environment (MOE) program, we identified RIPK1, RIPK3, and MLKL as potential targets of ligustroflavone. Further studies showed that the interaction between RIPK3 and RIPK1 or MLKL was significantly enhanced, which was blocked in the presence of ligustroflavone. Based on these observations, we conclude that ligustroflavone protects rat brain from ischemic injury, and its beneficial effect is related to the prevention of necroptosis through a mechanism involving targeting RIPK1, RIPK3, and/or MLKL. |
| doi_str_mv | 10.1007/s00210-019-01656-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2232110510</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2219822984</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-bc447fa91fbc76faae4f1bdd3972644792d1f7fb84dd0d7d5cb574ad346a9a0b3</originalsourceid><addsrcrecordid>eNp9kUtLAzEUhYMotlb_gAsJuHEzNjeZV5YiPoojiug6ZCbJdGo70yYZxX9vaquCCxd5wP3OuZd7EDoGcg6EZGNHCAUSEeDhpEka8R00hJjRCDjQXTQM9TwCyvMBOnBuRghJIUn20YABSZKU5kO0Kpq6d952Zi7fulZjq1VfaYdbXdlu6TvXONy02EqPSyvDTxqvLW5cNdWLpsJr7avGfmq7vp5iL22tfdPW-GnyeAfj9c3G98VdgZfST9_lxyHaM3Lu9NH2HaGX66vny9uoeLiZXF4UUcWyxEdlFceZkRxMWWWpkVLHBkqlGM9oGkqcKjCZKfNYKaIylVRlksVSsTiVXJKSjdDZxndpu1WvnReLMLSez2Wru94JShmFsAcgAT39g8663rZhukABz2lYYRwouqHCYpyz2oilbRbSfgggYh2I2AQiQiDiKxDBg-hka92XC61-JN8JBIBtABdKba3tb-9_bD8BpWuW5A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2219822984</pqid></control><display><type>article</type><title>Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway</title><source>SpringerNature Journals</source><creator>Zhang, Yi-Yue ; Liu, Wei-Ning ; Li, Yue-Qi ; Zhang, Xiao-Jie ; Yang, Jie ; Luo, Xiu-Ju ; Peng, Jun</creator><creatorcontrib>Zhang, Yi-Yue ; Liu, Wei-Ning ; Li, Yue-Qi ; Zhang, Xiao-Jie ; Yang, Jie ; Luo, Xiu-Ju ; Peng, Jun</creatorcontrib><description>Receptor-interacting protein kinase 1/3 (RIPK1/3) and mixed lineage kinase domain-like (MLKL)-mediated necroptosis contributes to brain injury after ischemic stroke. Ligustroflavone is an ingredient of
common privet
with activities of anti-inflammation and complement inhibition. This study aims to explore the effect of ligustroflavone on ischemic brain injury in stroke rat and the underlying mechanisms. A rat model of ischemic stroke was established by middle cerebral artery occlusion (MCAO), which showed ischemic injury (increase in neurological deficit score and infarct volume) and upregulation of necroptosis-associated proteins (RIPK1, RIPK3 and MLKL/p-MLKL). Administration of ligustroflavone (30 mg/kg, i.g.) 15 min before ischemia evidently improved neurological function, reduced infarct volume, and decreased the levels of necroptosis-associated proteins except the RIPK1. Consistently, hypoxia-cultured PC12 cells (O
2
/N2/CO
2
, 1:94:5, 8 h) caused cellular injury (LDH release and necroposis) concomitant with up-regulation of necroptosis-associated proteins, and these phenomena were blocked in the presence of ligustroflavone (25 μM) except the elevated RIPK1 levels. Using the Molecular Operating Environment (MOE) program, we identified RIPK1, RIPK3, and MLKL as potential targets of ligustroflavone. Further studies showed that the interaction between RIPK3 and RIPK1 or MLKL was significantly enhanced, which was blocked in the presence of ligustroflavone. Based on these observations, we conclude that ligustroflavone protects rat brain from ischemic injury, and its beneficial effect is related to the prevention of necroptosis through a mechanism involving targeting RIPK1, RIPK3, and/or MLKL.</description><identifier>ISSN: 0028-1298</identifier><identifier>EISSN: 1432-1912</identifier><identifier>DOI: 10.1007/s00210-019-01656-9</identifier><identifier>PMID: 31055628</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Brain ; Brain injury ; Carbon dioxide ; Cerebral blood flow ; Hypoxia ; Ischemia ; Kinases ; MAP kinase ; Necroptosis ; Neurosciences ; Occlusion ; Original Article ; Pharmacology/Toxicology ; Pheochromocytoma cells ; Protein kinase ; Proteins ; Rodents ; Stroke ; Traumatic brain injury</subject><ispartof>Naunyn-Schmiedeberg's archives of pharmacology, 2019-09, Vol.392 (9), p.1085-1095</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>Naunyn-Schmiedeberg's Archives of Pharmacology is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-bc447fa91fbc76faae4f1bdd3972644792d1f7fb84dd0d7d5cb574ad346a9a0b3</citedby><cites>FETCH-LOGICAL-c375t-bc447fa91fbc76faae4f1bdd3972644792d1f7fb84dd0d7d5cb574ad346a9a0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00210-019-01656-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00210-019-01656-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31055628$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yi-Yue</creatorcontrib><creatorcontrib>Liu, Wei-Ning</creatorcontrib><creatorcontrib>Li, Yue-Qi</creatorcontrib><creatorcontrib>Zhang, Xiao-Jie</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Luo, Xiu-Ju</creatorcontrib><creatorcontrib>Peng, Jun</creatorcontrib><title>Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway</title><title>Naunyn-Schmiedeberg's archives of pharmacology</title><addtitle>Naunyn-Schmiedeberg's Arch Pharmacol</addtitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><description>Receptor-interacting protein kinase 1/3 (RIPK1/3) and mixed lineage kinase domain-like (MLKL)-mediated necroptosis contributes to brain injury after ischemic stroke. Ligustroflavone is an ingredient of
common privet
with activities of anti-inflammation and complement inhibition. This study aims to explore the effect of ligustroflavone on ischemic brain injury in stroke rat and the underlying mechanisms. A rat model of ischemic stroke was established by middle cerebral artery occlusion (MCAO), which showed ischemic injury (increase in neurological deficit score and infarct volume) and upregulation of necroptosis-associated proteins (RIPK1, RIPK3 and MLKL/p-MLKL). Administration of ligustroflavone (30 mg/kg, i.g.) 15 min before ischemia evidently improved neurological function, reduced infarct volume, and decreased the levels of necroptosis-associated proteins except the RIPK1. Consistently, hypoxia-cultured PC12 cells (O
2
/N2/CO
2
, 1:94:5, 8 h) caused cellular injury (LDH release and necroposis) concomitant with up-regulation of necroptosis-associated proteins, and these phenomena were blocked in the presence of ligustroflavone (25 μM) except the elevated RIPK1 levels. Using the Molecular Operating Environment (MOE) program, we identified RIPK1, RIPK3, and MLKL as potential targets of ligustroflavone. Further studies showed that the interaction between RIPK3 and RIPK1 or MLKL was significantly enhanced, which was blocked in the presence of ligustroflavone. Based on these observations, we conclude that ligustroflavone protects rat brain from ischemic injury, and its beneficial effect is related to the prevention of necroptosis through a mechanism involving targeting RIPK1, RIPK3, and/or MLKL.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Brain injury</subject><subject>Carbon dioxide</subject><subject>Cerebral blood flow</subject><subject>Hypoxia</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>Necroptosis</subject><subject>Neurosciences</subject><subject>Occlusion</subject><subject>Original Article</subject><subject>Pharmacology/Toxicology</subject><subject>Pheochromocytoma cells</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Stroke</subject><subject>Traumatic brain injury</subject><issn>0028-1298</issn><issn>1432-1912</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUtLAzEUhYMotlb_gAsJuHEzNjeZV5YiPoojiug6ZCbJdGo70yYZxX9vaquCCxd5wP3OuZd7EDoGcg6EZGNHCAUSEeDhpEka8R00hJjRCDjQXTQM9TwCyvMBOnBuRghJIUn20YABSZKU5kO0Kpq6d952Zi7fulZjq1VfaYdbXdlu6TvXONy02EqPSyvDTxqvLW5cNdWLpsJr7avGfmq7vp5iL22tfdPW-GnyeAfj9c3G98VdgZfST9_lxyHaM3Lu9NH2HaGX66vny9uoeLiZXF4UUcWyxEdlFceZkRxMWWWpkVLHBkqlGM9oGkqcKjCZKfNYKaIylVRlksVSsTiVXJKSjdDZxndpu1WvnReLMLSez2Wru94JShmFsAcgAT39g8663rZhukABz2lYYRwouqHCYpyz2oilbRbSfgggYh2I2AQiQiDiKxDBg-hka92XC61-JN8JBIBtABdKba3tb-9_bD8BpWuW5A</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Zhang, Yi-Yue</creator><creator>Liu, Wei-Ning</creator><creator>Li, Yue-Qi</creator><creator>Zhang, Xiao-Jie</creator><creator>Yang, Jie</creator><creator>Luo, Xiu-Ju</creator><creator>Peng, Jun</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20190901</creationdate><title>Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway</title><author>Zhang, Yi-Yue ; Liu, Wei-Ning ; Li, Yue-Qi ; Zhang, Xiao-Jie ; Yang, Jie ; Luo, Xiu-Ju ; Peng, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-bc447fa91fbc76faae4f1bdd3972644792d1f7fb84dd0d7d5cb574ad346a9a0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain injury</topic><topic>Carbon dioxide</topic><topic>Cerebral blood flow</topic><topic>Hypoxia</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>Necroptosis</topic><topic>Neurosciences</topic><topic>Occlusion</topic><topic>Original Article</topic><topic>Pharmacology/Toxicology</topic><topic>Pheochromocytoma cells</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Rodents</topic><topic>Stroke</topic><topic>Traumatic brain injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yi-Yue</creatorcontrib><creatorcontrib>Liu, Wei-Ning</creatorcontrib><creatorcontrib>Li, Yue-Qi</creatorcontrib><creatorcontrib>Zhang, Xiao-Jie</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Luo, Xiu-Ju</creatorcontrib><creatorcontrib>Peng, Jun</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yi-Yue</au><au>Liu, Wei-Ning</au><au>Li, Yue-Qi</au><au>Zhang, Xiao-Jie</au><au>Yang, Jie</au><au>Luo, Xiu-Ju</au><au>Peng, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway</atitle><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle><stitle>Naunyn-Schmiedeberg's Arch Pharmacol</stitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>392</volume><issue>9</issue><spage>1085</spage><epage>1095</epage><pages>1085-1095</pages><issn>0028-1298</issn><eissn>1432-1912</eissn><abstract>Receptor-interacting protein kinase 1/3 (RIPK1/3) and mixed lineage kinase domain-like (MLKL)-mediated necroptosis contributes to brain injury after ischemic stroke. Ligustroflavone is an ingredient of
common privet
with activities of anti-inflammation and complement inhibition. This study aims to explore the effect of ligustroflavone on ischemic brain injury in stroke rat and the underlying mechanisms. A rat model of ischemic stroke was established by middle cerebral artery occlusion (MCAO), which showed ischemic injury (increase in neurological deficit score and infarct volume) and upregulation of necroptosis-associated proteins (RIPK1, RIPK3 and MLKL/p-MLKL). Administration of ligustroflavone (30 mg/kg, i.g.) 15 min before ischemia evidently improved neurological function, reduced infarct volume, and decreased the levels of necroptosis-associated proteins except the RIPK1. Consistently, hypoxia-cultured PC12 cells (O
2
/N2/CO
2
, 1:94:5, 8 h) caused cellular injury (LDH release and necroposis) concomitant with up-regulation of necroptosis-associated proteins, and these phenomena were blocked in the presence of ligustroflavone (25 μM) except the elevated RIPK1 levels. Using the Molecular Operating Environment (MOE) program, we identified RIPK1, RIPK3, and MLKL as potential targets of ligustroflavone. Further studies showed that the interaction between RIPK3 and RIPK1 or MLKL was significantly enhanced, which was blocked in the presence of ligustroflavone. Based on these observations, we conclude that ligustroflavone protects rat brain from ischemic injury, and its beneficial effect is related to the prevention of necroptosis through a mechanism involving targeting RIPK1, RIPK3, and/or MLKL.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31055628</pmid><doi>10.1007/s00210-019-01656-9</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-1298 |
| ispartof | Naunyn-Schmiedeberg's archives of pharmacology, 2019-09, Vol.392 (9), p.1085-1095 |
| issn | 0028-1298 1432-1912 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2232110510 |
| source | SpringerNature Journals |
| subjects | Biomedical and Life Sciences Biomedicine Brain Brain injury Carbon dioxide Cerebral blood flow Hypoxia Ischemia Kinases MAP kinase Necroptosis Neurosciences Occlusion Original Article Pharmacology/Toxicology Pheochromocytoma cells Protein kinase Proteins Rodents Stroke Traumatic brain injury |
| title | Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T09%3A07%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ligustroflavone%20reduces%20necroptosis%20in%20rat%20brain%20after%20ischemic%20stroke%20through%20targeting%20RIPK1/RIPK3/MLKL%20pathway&rft.jtitle=Naunyn-Schmiedeberg's%20archives%20of%20pharmacology&rft.au=Zhang,%20Yi-Yue&rft.date=2019-09-01&rft.volume=392&rft.issue=9&rft.spage=1085&rft.epage=1095&rft.pages=1085-1095&rft.issn=0028-1298&rft.eissn=1432-1912&rft_id=info:doi/10.1007/s00210-019-01656-9&rft_dat=%3Cproquest_cross%3E2219822984%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2219822984&rft_id=info:pmid/31055628&rfr_iscdi=true |