{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:17:19Z","timestamp":1792675039396,"version":"4.5.0"},"reference-count":68,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2022YFE0131000"],"award-info":[{"award-number":["2022YFE0131000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82220108012"],"award-info":[{"award-number":["82220108012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20220096"],"award-info":[{"award-number":["BK20220096"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010023","name":"Natural Science Research of Jiangsu Higher Education Institutions of China","doi-asserted-by":"publisher","award":["22KJB320007"],"award-info":[{"award-number":["22KJB320007"]}],"id":[{"id":"10.13039\/501100010023","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of\n                    <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                    , is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH\u2010induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood\u2010induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons. Single\u2010cell nuclear sequencing reveals that the cyclic adenosine monophosphate (cAMP)\/cAMP\u2010activated exchange protein\u20101 (EPAC\u20101) signaling pathways are impacted by celastrol. Celastrol binds to cNMP (a domain of EPAC\u20101) to inhibit its interaction with voltage\u2010dependent anion\u2010selective channel protein 1 (VDAC1) and blocks the opening of mitochondrial permeability transition pores. After neuron\u2010specific knockout of EPAC1, the neuroprotective effects of celastrol are diminished. In summary, this study demonstrates that celastrol, through its interaction with EPAC\u20101, ameliorates mitochondrial dysfunction in neurons, thus potentially improving SBI induced by ICH. These findings suggest that targeting EPAC\u20101 with celastrol can be a promising therapeutic approach for treating ICH\u2010induced SBI.\n                  <\/jats:p>","DOI":"10.1002\/advs.202307556","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T05:23:17Z","timestamp":1710393797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Celastrol Ameliorates Neuronal Mitochondrial Dysfunction Induced by Intracerebral Hemorrhage via Targeting cAMP\u2010Activated Exchange Protein\u20101"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-5847","authenticated-orcid":false,"suffix":"Sr.","given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery &amp; Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Institute of Stroke Research Soochow University  188 Shizi Street Suzhou 215006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  168 Xianlin Avenue Nanjing 210023 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guannan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery &amp; Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Institute of Stroke Research Soochow University  188 Shizi Street Suzhou 215006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrong","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery &amp; Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Institute of Stroke Research Soochow University  188 Shizi Street Suzhou 215006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery &amp; Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Institute of Stroke Research Soochow University  188 Shizi Street Suzhou 215006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery &amp; Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Institute of Stroke Research Soochow University  188 Shizi Street Suzhou 215006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery &amp; Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Institute of Stroke Research Soochow University  188 Shizi Street Suzhou 215006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingshun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaobo","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Cao","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Tao","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou 215123 China"},{"name":"Department of Physiology and Neurobiology Medical College of Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Cheng","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology School of Medicine Loma Linda University  Loma Linda CA 92350 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0758-1907","authenticated-orcid":false,"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery &amp; Brain and Nerve Research Laboratory The First Affiliated Hospital of Soochow University  188 Shizi Street Suzhou 215006 China"},{"name":"Institute of Stroke Research Soochow University  188 Shizi Street Suzhou 215006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319949"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70104-7"},{"key":"e_1_2_9_1_3","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18769513"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00424-7"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00252-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70025-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.46728"},{"key":"e_1_2_9_4_2","first-page":"5373","volume":"37","author":"Georgieva E.","year":"2017","journal-title":"Anticancer Res."},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000240674.99945.4e"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2592935"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153398"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01231-4"},{"key":"e_1_2_9_7_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2022.12.002"},{"key":"e_1_2_9_7_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.08.005"},{"key":"e_1_2_9_7_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.011"},{"key":"e_1_2_9_7_6","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0358-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.09.031"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2022.116099"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.03.008"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26295-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.01.043"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1124-6"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102134"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2046437"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.11.029"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1159\/000090364"},{"key":"e_1_2_9_14_3","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203221"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.12.008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.010909.105714"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1197"},{"key":"e_1_2_9_16_3","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013070679"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1416163112"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516036113"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103880"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-022-00381-4"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22454-z"},{"key":"e_1_2_9_20_3","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02216-w"},{"key":"e_1_2_9_20_4","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11081597"},{"key":"e_1_2_9_20_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.01.017"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12936"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010048"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.114623"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25703"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.847246"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.615451"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00004.2013"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/24884"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24477"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309859"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4444"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18774666"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17753590"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz5752"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2018497117"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-015-0245-z"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18785480"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.09.015"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-019-0543-8"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1064-1"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.10.011"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.919731"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110044"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-22-0026"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.58.2.0010"}],"updated-by":[{"DOI":"10.1002\/advs.202406154","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000}}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202307556","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:15:45Z","timestamp":1759958145000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202307556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,14]]},"references-count":68,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/advs.202307556"],"URL":"https:\/\/doi.org\/10.1002\/advs.202307556","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,14]]},"assertion":[{"value":"2023-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2307556"}}