Catalpol alleviates hypoxia ischemia-induced brain damage by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis in neonatal rats
Hypoxic-ischemic encephalopathy (HIE) is a brain damage caused by perinatal hypoxia and blood flow reduction. Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the...
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| Veröffentlicht in: | European journal of pharmacology 2024-04, Vol.968, p.176406-176406, Article 176406 |
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| container_title | European journal of pharmacology |
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| creator | Lin, Jingjing Deng, Lu Qi, Ailin Jiang, Hong Xu, Di Zheng, Yuehui Zhang, Zixuan Guo, Xiaoman Hu, Beilei Li, Peijun |
| description | Hypoxic-ischemic encephalopathy (HIE) is a brain damage caused by perinatal hypoxia and blood flow reduction. Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa, has antioxidant and neuroprotective effects. This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose deprivation. The ferroptosis inducer erastin reversed the protective effects of catalpol both in vitro and in vivo. We concluded that catalpol protects against hypoxic-ischemic brain damage (HIBD) by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis. |
| doi_str_mv | 10.1016/j.ejphar.2024.176406 |
| format | Article |
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Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa, has antioxidant and neuroprotective effects. This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose deprivation. The ferroptosis inducer erastin reversed the protective effects of catalpol both in vitro and in vivo. We concluded that catalpol protects against hypoxic-ischemic brain damage (HIBD) by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2024.176406</identifier><identifier>PMID: 38341076</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Animals, Newborn ; Brain - metabolism ; Catalpol ; Ferroptosis ; Hypoxia ; Hypoxia-Ischemia, Brain - complications ; Hypoxia-Ischemia, Brain - drug therapy ; Hypoxia-Ischemia, Brain - metabolism ; Hypoxic-ischemic encephalopathy ; Iridoid Glucosides - pharmacology ; Iridoid Glucosides - therapeutic use ; Ischemia ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; NF-E2-Related Factor 2 - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; PI3K/NRF2/System Xc-/GPX4 axis ; Rats</subject><ispartof>European journal of pharmacology, 2024-04, Vol.968, p.176406-176406, Article 176406</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c357t-30e97d58de57705e5926a3b43ad0412f054ac73a8b2be469623aee6f74d46fd03</cites><orcidid>0000-0001-5429-3337 ; 0000-0003-0043-6560 ; 0000-0003-0701-3122</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2024.176406$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38341076$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Jingjing</creatorcontrib><creatorcontrib>Deng, Lu</creatorcontrib><creatorcontrib>Qi, Ailin</creatorcontrib><creatorcontrib>Jiang, Hong</creatorcontrib><creatorcontrib>Xu, Di</creatorcontrib><creatorcontrib>Zheng, Yuehui</creatorcontrib><creatorcontrib>Zhang, Zixuan</creatorcontrib><creatorcontrib>Guo, Xiaoman</creatorcontrib><creatorcontrib>Hu, Beilei</creatorcontrib><creatorcontrib>Li, Peijun</creatorcontrib><title>Catalpol alleviates hypoxia ischemia-induced brain damage by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis in neonatal rats</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Hypoxic-ischemic encephalopathy (HIE) is a brain damage caused by perinatal hypoxia and blood flow reduction. Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa, has antioxidant and neuroprotective effects. This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose deprivation. The ferroptosis inducer erastin reversed the protective effects of catalpol both in vitro and in vivo. We concluded that catalpol protects against hypoxic-ischemic brain damage (HIBD) by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Brain - metabolism</subject><subject>Catalpol</subject><subject>Ferroptosis</subject><subject>Hypoxia</subject><subject>Hypoxia-Ischemia, Brain - complications</subject><subject>Hypoxia-Ischemia, Brain - drug therapy</subject><subject>Hypoxia-Ischemia, Brain - metabolism</subject><subject>Hypoxic-ischemic encephalopathy</subject><subject>Iridoid Glucosides - pharmacology</subject><subject>Iridoid Glucosides - therapeutic use</subject><subject>Ischemia</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>PI3K/NRF2/System Xc-/GPX4 axis</subject><subject>Rats</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EokPpGyDkJZvM-C_xZIOERrRUVLSqqNSddRPfTDzKH7ZTdZ6CV8ajFJas7ua7595zDiEfOFtzxovNYY2HqQW_FkyoNdeFYsUrsuJbXWZMc_GarBjjKhNlWZ6RdyEcGGN5KfK35ExupeJMFyvyewcRumnsKHQdPjmIGGh7nMZnB9SFusXeQeYGO9doaeXBDdRCD3uk1ZG6oXWVi27Y0wa9H6c4BhdobP0479s0kd5dy--bH_eXYhOOIWJPH-tsc3X3qCg8JzTJDTgOpyeohxjekzcNdAEvXuY5ebj8-nP3Lbu5vbrefbnJapnrmEmGpbb51mKuNcsx-SpAVkqCZYqLhuUKai1hW4kKVVEWQgJi0WhlVdFYJs_Jp0V38uOvGUM0fXKLXQfpnTkYkYJiUnKZJ1QtaO3HEDw2ZvKuB380nJlTFeZglirMqQqzVJHWPr5cmKse7b-lv9kn4PMCYPL55NCbUDscUs7OYx2NHd3_L_wBgMadGw</recordid><startdate>20240405</startdate><enddate>20240405</enddate><creator>Lin, Jingjing</creator><creator>Deng, Lu</creator><creator>Qi, Ailin</creator><creator>Jiang, Hong</creator><creator>Xu, Di</creator><creator>Zheng, Yuehui</creator><creator>Zhang, Zixuan</creator><creator>Guo, Xiaoman</creator><creator>Hu, Beilei</creator><creator>Li, Peijun</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><orcidid>https://orcid.org/0000-0001-5429-3337</orcidid><orcidid>https://orcid.org/0000-0003-0043-6560</orcidid><orcidid>https://orcid.org/0000-0003-0701-3122</orcidid></search><sort><creationdate>20240405</creationdate><title>Catalpol alleviates hypoxia ischemia-induced brain damage by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis in neonatal rats</title><author>Lin, Jingjing ; Deng, Lu ; Qi, Ailin ; Jiang, Hong ; Xu, Di ; Zheng, Yuehui ; Zhang, Zixuan ; Guo, Xiaoman ; Hu, Beilei ; Li, Peijun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-30e97d58de57705e5926a3b43ad0412f054ac73a8b2be469623aee6f74d46fd03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Brain - metabolism</topic><topic>Catalpol</topic><topic>Ferroptosis</topic><topic>Hypoxia</topic><topic>Hypoxia-Ischemia, Brain - complications</topic><topic>Hypoxia-Ischemia, Brain - drug therapy</topic><topic>Hypoxia-Ischemia, Brain - metabolism</topic><topic>Hypoxic-ischemic encephalopathy</topic><topic>Iridoid Glucosides - pharmacology</topic><topic>Iridoid Glucosides - therapeutic use</topic><topic>Ischemia</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>PI3K/NRF2/System Xc-/GPX4 axis</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Jingjing</creatorcontrib><creatorcontrib>Deng, Lu</creatorcontrib><creatorcontrib>Qi, Ailin</creatorcontrib><creatorcontrib>Jiang, Hong</creatorcontrib><creatorcontrib>Xu, Di</creatorcontrib><creatorcontrib>Zheng, Yuehui</creatorcontrib><creatorcontrib>Zhang, Zixuan</creatorcontrib><creatorcontrib>Guo, Xiaoman</creatorcontrib><creatorcontrib>Hu, Beilei</creatorcontrib><creatorcontrib>Li, Peijun</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect: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>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Jingjing</au><au>Deng, Lu</au><au>Qi, Ailin</au><au>Jiang, Hong</au><au>Xu, Di</au><au>Zheng, Yuehui</au><au>Zhang, Zixuan</au><au>Guo, Xiaoman</au><au>Hu, Beilei</au><au>Li, Peijun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Catalpol alleviates hypoxia ischemia-induced brain damage by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis in neonatal rats</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2024-04-05</date><risdate>2024</risdate><volume>968</volume><spage>176406</spage><epage>176406</epage><pages>176406-176406</pages><artnum>176406</artnum><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>Hypoxic-ischemic encephalopathy (HIE) is a brain damage caused by perinatal hypoxia and blood flow reduction. Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa, has antioxidant and neuroprotective effects. This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose deprivation. The ferroptosis inducer erastin reversed the protective effects of catalpol both in vitro and in vivo. We concluded that catalpol protects against hypoxic-ischemic brain damage (HIBD) by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>38341076</pmid><doi>10.1016/j.ejphar.2024.176406</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5429-3337</orcidid><orcidid>https://orcid.org/0000-0003-0043-6560</orcidid><orcidid>https://orcid.org/0000-0003-0701-3122</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Newborn Brain - metabolism Catalpol Ferroptosis Hypoxia Hypoxia-Ischemia, Brain - complications Hypoxia-Ischemia, Brain - drug therapy Hypoxia-Ischemia, Brain - metabolism Hypoxic-ischemic encephalopathy Iridoid Glucosides - pharmacology Iridoid Glucosides - therapeutic use Ischemia Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use NF-E2-Related Factor 2 - metabolism Phosphatidylinositol 3-Kinases - metabolism PI3K/NRF2/System Xc-/GPX4 axis Rats |
| title | Catalpol alleviates hypoxia ischemia-induced brain damage by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis in neonatal rats |
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