Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway
Palmatine (PAL), a natural isoquinoline alkaloid, possesses extensive biological and pharmaceutical activities, including antioxidative stress, anti-inflammatory, antitumor, neuroprotective, and gastroprotective activities. However, it is unknown whether PAL has a protective effect against ischemic...
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| Veröffentlicht in: | Oxidative medicine and cellular longevity 2021, Vol.2021 (1), p.6660193-6660193 |
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| container_title | Oxidative medicine and cellular longevity |
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| creator | Tang, Chaoliang Hong, Junmou Hu, Chengyun Huang, Chunxia Gao, Jie Huang, Jun Wang, Di Geng, Qingtian Dong, Yongfei |
| description | Palmatine (PAL), a natural isoquinoline alkaloid, possesses extensive biological and pharmaceutical activities, including antioxidative stress, anti-inflammatory, antitumor, neuroprotective, and gastroprotective activities. However, it is unknown whether PAL has a protective effect against ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. In the present study, a transient middle cerebral artery occlusion (MCAO) mouse model was used to mimic ischemic stroke and cerebral I/R injury in mice. Our study demonstrated that PAL treatment ameliorated cerebral I/R injury by decreasing infarct volume, neurological scores, and brain water content. PAL administration attenuated oxidative stress, the inflammatory response, and neuronal apoptosis in mice after cerebral I/R injury. In addition, PAL treatment also decreases hypoxia and reperfusion- (H/R-) induced neuronal injury by reducing oxidative stress, the inflammatory response, and neuronal apoptosis. Moreover, the neuroprotective effects of PAL were associated with the activation of the AMP-activated protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown offsets PAL-mediated antioxidative stress and anti-inflammatory effects. Therefore, our results suggest that PAL may be a novel treatment strategy for ischemic stroke and cerebral I/R injury. |
| doi_str_mv | 10.1155/2021/6660193 |
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However, it is unknown whether PAL has a protective effect against ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. In the present study, a transient middle cerebral artery occlusion (MCAO) mouse model was used to mimic ischemic stroke and cerebral I/R injury in mice. Our study demonstrated that PAL treatment ameliorated cerebral I/R injury by decreasing infarct volume, neurological scores, and brain water content. PAL administration attenuated oxidative stress, the inflammatory response, and neuronal apoptosis in mice after cerebral I/R injury. In addition, PAL treatment also decreases hypoxia and reperfusion- (H/R-) induced neuronal injury by reducing oxidative stress, the inflammatory response, and neuronal apoptosis. Moreover, the neuroprotective effects of PAL were associated with the activation of the AMP-activated protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown offsets PAL-mediated antioxidative stress and anti-inflammatory effects. Therefore, our results suggest that PAL may be a novel treatment strategy for ischemic stroke and cerebral I/R injury.</description><identifier>ISSN: 1942-0900</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2021/6660193</identifier><identifier>PMID: 33777318</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>AMP-Activated Protein Kinases - metabolism ; Apoptosis ; Brain research ; Cerebrovascular Disorders - metabolism ; Cerebrovascular Disorders - pathology ; Cerebrovascular Disorders - prevention & control ; Cytokines ; Hypoxia ; Ischemia ; Kinases ; NF-E2-Related Factor 2 - metabolism ; omega-Chloroacetophenone ; Oxidative stress ; Palmitates - pharmacology ; Reperfusion Injury - metabolism ; Reperfusion Injury - pathology ; Reperfusion Injury - prevention & control ; Signal Transduction - drug effects ; Tumor necrosis factor-TNF ; Variance analysis</subject><ispartof>Oxidative medicine and cellular longevity, 2021, Vol.2021 (1), p.6660193-6660193</ispartof><rights>Copyright © 2021 Chaoliang Tang et al.</rights><rights>Copyright © 2021 Chaoliang Tang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 Chaoliang Tang et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-47d7d1cf261e7701de45778d6681d86da3284d1672fda19d41befa80aa7315f63</citedby><cites>FETCH-LOGICAL-c448t-47d7d1cf261e7701de45778d6681d86da3284d1672fda19d41befa80aa7315f63</cites><orcidid>0000-0002-6873-7821 ; 0000-0002-1740-1375</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981182/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981182/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33777318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Xu, Shi Yuan</contributor><contributor>Shi Yuan Xu</contributor><creatorcontrib>Tang, Chaoliang</creatorcontrib><creatorcontrib>Hong, Junmou</creatorcontrib><creatorcontrib>Hu, Chengyun</creatorcontrib><creatorcontrib>Huang, Chunxia</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Huang, Jun</creatorcontrib><creatorcontrib>Wang, Di</creatorcontrib><creatorcontrib>Geng, Qingtian</creatorcontrib><creatorcontrib>Dong, Yongfei</creatorcontrib><title>Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway</title><title>Oxidative medicine and cellular longevity</title><addtitle>Oxid Med Cell Longev</addtitle><description>Palmatine (PAL), a natural isoquinoline alkaloid, possesses extensive biological and pharmaceutical activities, including antioxidative stress, anti-inflammatory, antitumor, neuroprotective, and gastroprotective activities. However, it is unknown whether PAL has a protective effect against ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. In the present study, a transient middle cerebral artery occlusion (MCAO) mouse model was used to mimic ischemic stroke and cerebral I/R injury in mice. Our study demonstrated that PAL treatment ameliorated cerebral I/R injury by decreasing infarct volume, neurological scores, and brain water content. PAL administration attenuated oxidative stress, the inflammatory response, and neuronal apoptosis in mice after cerebral I/R injury. In addition, PAL treatment also decreases hypoxia and reperfusion- (H/R-) induced neuronal injury by reducing oxidative stress, the inflammatory response, and neuronal apoptosis. Moreover, the neuroprotective effects of PAL were associated with the activation of the AMP-activated protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown offsets PAL-mediated antioxidative stress and anti-inflammatory effects. Therefore, our results suggest that PAL may be a novel treatment strategy for ischemic stroke and cerebral I/R injury.</description><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Apoptosis</subject><subject>Brain research</subject><subject>Cerebrovascular Disorders - metabolism</subject><subject>Cerebrovascular Disorders - pathology</subject><subject>Cerebrovascular Disorders - prevention & control</subject><subject>Cytokines</subject><subject>Hypoxia</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>omega-Chloroacetophenone</subject><subject>Oxidative stress</subject><subject>Palmitates - pharmacology</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - pathology</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Signal Transduction - drug effects</subject><subject>Tumor necrosis factor-TNF</subject><subject>Variance analysis</subject><issn>1942-0900</issn><issn>1942-0994</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc2LEzEYh4Mo7rp68ywBL4LW5muSzEUoxY_iqkX0HNJJspMyk3STzC79701pLerBU17yPjy8P34APMfoLcZNMyeI4DnnHOGWPgCXuGVkhtqWPTzPCF2AJzlvEeKUMPwYXFAqhKBYXgK31sOoiw8WrlMstisZ6hvtQy5waZPdJD3AVe56O3o9_253Nrkp-xjgKmyntIebPVx0xd9VR_2MDpbewsWX9ef51-QIXOvS3-v9U_DI6SHbZ6f3Cvz88P7H8tPs-tvH1XJxPesYk2XGhBEGd45wbIVA2FjWCCEN5xIbyY2mRDKDuSDOaNwahjfWaYm0rmkax-kVeHf07qbNaE1nQ6kB1C75Uae9itqrvzfB9-om3inRSowlqYJXJ0GKt5PNRY0-d3YYdLBxyoo0iDeokUxU9OU_6DZOKdR4B4rShoiWVerNkepSzDlZdz4GI3UoUB0KVKcCK_7izwBn-HdjFXh9BHofjL73_9f9Alcioto</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Tang, Chaoliang</creator><creator>Hong, Junmou</creator><creator>Hu, Chengyun</creator><creator>Huang, Chunxia</creator><creator>Gao, Jie</creator><creator>Huang, Jun</creator><creator>Wang, Di</creator><creator>Geng, Qingtian</creator><creator>Dong, Yongfei</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6873-7821</orcidid><orcidid>https://orcid.org/0000-0002-1740-1375</orcidid></search><sort><creationdate>2021</creationdate><title>Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway</title><author>Tang, Chaoliang ; Hong, Junmou ; Hu, Chengyun ; Huang, Chunxia ; Gao, Jie ; Huang, Jun ; Wang, Di ; Geng, Qingtian ; Dong, Yongfei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-47d7d1cf261e7701de45778d6681d86da3284d1672fda19d41befa80aa7315f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Apoptosis</topic><topic>Brain research</topic><topic>Cerebrovascular Disorders - metabolism</topic><topic>Cerebrovascular Disorders - pathology</topic><topic>Cerebrovascular Disorders - prevention & control</topic><topic>Cytokines</topic><topic>Hypoxia</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>omega-Chloroacetophenone</topic><topic>Oxidative stress</topic><topic>Palmitates - pharmacology</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - pathology</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Signal Transduction - drug effects</topic><topic>Tumor necrosis factor-TNF</topic><topic>Variance analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Chaoliang</creatorcontrib><creatorcontrib>Hong, Junmou</creatorcontrib><creatorcontrib>Hu, Chengyun</creatorcontrib><creatorcontrib>Huang, Chunxia</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Huang, Jun</creatorcontrib><creatorcontrib>Wang, Di</creatorcontrib><creatorcontrib>Geng, Qingtian</creatorcontrib><creatorcontrib>Dong, Yongfei</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content 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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oxidative medicine and cellular longevity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Chaoliang</au><au>Hong, Junmou</au><au>Hu, Chengyun</au><au>Huang, Chunxia</au><au>Gao, Jie</au><au>Huang, Jun</au><au>Wang, Di</au><au>Geng, Qingtian</au><au>Dong, Yongfei</au><au>Xu, Shi Yuan</au><au>Shi Yuan Xu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway</atitle><jtitle>Oxidative medicine and cellular longevity</jtitle><addtitle>Oxid Med Cell Longev</addtitle><date>2021</date><risdate>2021</risdate><volume>2021</volume><issue>1</issue><spage>6660193</spage><epage>6660193</epage><pages>6660193-6660193</pages><issn>1942-0900</issn><eissn>1942-0994</eissn><abstract>Palmatine (PAL), a natural isoquinoline alkaloid, possesses extensive biological and pharmaceutical activities, including antioxidative stress, anti-inflammatory, antitumor, neuroprotective, and gastroprotective activities. However, it is unknown whether PAL has a protective effect against ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. In the present study, a transient middle cerebral artery occlusion (MCAO) mouse model was used to mimic ischemic stroke and cerebral I/R injury in mice. Our study demonstrated that PAL treatment ameliorated cerebral I/R injury by decreasing infarct volume, neurological scores, and brain water content. PAL administration attenuated oxidative stress, the inflammatory response, and neuronal apoptosis in mice after cerebral I/R injury. In addition, PAL treatment also decreases hypoxia and reperfusion- (H/R-) induced neuronal injury by reducing oxidative stress, the inflammatory response, and neuronal apoptosis. Moreover, the neuroprotective effects of PAL were associated with the activation of the AMP-activated protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown offsets PAL-mediated antioxidative stress and anti-inflammatory effects. Therefore, our results suggest that PAL may be a novel treatment strategy for ischemic stroke and cerebral I/R injury.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>33777318</pmid><doi>10.1155/2021/6660193</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-6873-7821</orcidid><orcidid>https://orcid.org/0000-0002-1740-1375</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | AMP-Activated Protein Kinases - metabolism Apoptosis Brain research Cerebrovascular Disorders - metabolism Cerebrovascular Disorders - pathology Cerebrovascular Disorders - prevention & control Cytokines Hypoxia Ischemia Kinases NF-E2-Related Factor 2 - metabolism omega-Chloroacetophenone Oxidative stress Palmitates - pharmacology Reperfusion Injury - metabolism Reperfusion Injury - pathology Reperfusion Injury - prevention & control Signal Transduction - drug effects Tumor necrosis factor-TNF Variance analysis |
| title | Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway |
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