{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:29:30Z","timestamp":1791430170241,"version":"4.3.3"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973503"],"award-info":[{"award-number":["81973503"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174001"],"award-info":[{"award-number":["82174001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2019J01345"],"award-info":[{"award-number":["2019J01345"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2020J01727"],"award-info":[{"award-number":["2020J01727"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J02014"],"award-info":[{"award-number":["2021J02014"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Salidroside, a principal bioactive component of\n                    <jats:italic>Rhodiola crenulata<\/jats:italic>\n                    , is neuroprotective across a wide time window in stroke models. We investigated whether salidroside induced neurogenesis after cerebral ischemia and aimed to identify its primary molecular targets. Rats, subjected to transient 2\u2009h of middle cerebral artery occlusion (MCAO), received intraperitoneal vehicle or salidroside \u00b1 intracerebroventricular HSC70 inhibitor VER155008 or TrkB inhibitor ANA\u201012 for up to 7\u2009days. MRI, behavioural tests, immunofluorescent staining and western blotting measured effects of salidroside. Reverse virtual docking and enzymatic assays assessed interaction of salidroside with purified recombinant HSC70. Salidroside dose\u2010dependently decreased cerebral infarct volumes and neurological deficits, with maximal effects by 50\u2009mg\/kg\/day. This dose also improved performance in beam balance and Morris water maze tests. Salidroside significantly increased BrdU\n                    <jats:sup>+<\/jats:sup>\n                    \/nestin\n                    <jats:sup>+<\/jats:sup>\n                    , BrdU\n                    <jats:sup>+<\/jats:sup>\n                    \/DCX\n                    <jats:sup>+<\/jats:sup>\n                    , BrdU\n                    <jats:sup>+<\/jats:sup>\n                    \/NeuN\n                    <jats:sup>+<\/jats:sup>\n                    , BrdU\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/NeuN\n                    <jats:sup>+<\/jats:sup>\n                    and BDNF\n                    <jats:sup>+<\/jats:sup>\n                    cells in the peri\u2010infarct cortex, with less effect in striatum and no significant effect in the subventricular zone. Salidroside was predicted to bind with HSC70. Salidroside dose\u2010dependently increased HSC70 ATPase and HSC70\u2010dependent luciferase activities, but it did not activate HSP70. HSC70 immunoreactivity concentrated in the peri\u2010infarct cortex and was unchanged by salidroside. However, VER155008 prevented salidroside\u2010dependent increases of neurogenesis, BrdU\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/NeuN\n                    <jats:sup>+<\/jats:sup>\n                    cells and BDNF\n                    <jats:sup>+<\/jats:sup>\n                    cells in peri\u2010infarct cortex. Salidroside also increased BDNF protein and p\u2010TrkB\/TrkB ratio in ischemic brain, changes prevented by VER155008 and ANA\u201012, respectively. Additionally, ANA\u201012 blocked salidroside\u2010dependent neurogenesis and increased BrdU\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/NeuN\n                    <jats:sup>+<\/jats:sup>\n                    cells in the peri\u2010infarct cortex. Salidroside directly activates HSC70, thereby stimulating neurogenesis and neuroprotection via BDNF\/TrkB signalling after MCAO. Salidroside and similar activators of HSC70 might provide clinical therapies for ischemic stroke.\n                  <\/jats:p>","DOI":"10.1002\/ptr.8178","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T02:24:57Z","timestamp":1710555897000},"page":"2619-2640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Salidroside directly activates\n                    <scp>HSC70<\/scp>\n                    , revealing a new role for\n                    <scp>HSC70<\/scp>\n                    in\n                    <scp>BDNF<\/scp>\n                    signalling and neurogenesis after cerebral ischemia"],"prefix":"10.1002","volume":"38","author":[{"given":"Wenfang","family":"Lai","sequence":"first","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshuang","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelin","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Brown","sequence":"additional","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3932-4777","authenticated-orcid":false,"given":"Guizhu","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacology Fujian University of Traditional Chinese Medicine  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6773"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0b013e31825b9eb5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0448-19.2020"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.16"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00207-0"},{"key":"e_1_2_9_7_1","first-page":"8","article-title":"Motor coordination and balance in rodents","volume":"8","author":"Carter R. J.","year":"2001","journal-title":"Current Protocols in Neuroscience"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43992"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.700297"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2007.08.020"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfda.2015.04.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200407053"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-020-01159-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110458"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.974775"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19991011)413:1<146::AID-CNE10>3.0.CO;2-B"},{"issue":"131","key":"e_1_2_9_17_1","first-page":"56044","article-title":"Detecting behavioral deficits in rats after traumatic brain injury","volume":"30","author":"Hausser N.","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.510982"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-9045-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.081011098"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00159-3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14112330"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0001-6"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134642"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025760"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1179\/174313209X383312"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-015-9529-9"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759091414558417"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-387332"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(01)00657-8"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114417"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811825116"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019034"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-5752"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1081-0"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12581"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.1.84"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00821"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(84)90007-4"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01683.x"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4323-06.2006"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.21-0120"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113518"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-7-77"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-020-00841-w"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0133-3"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078443"},{"key":"e_1_2_9_49_1","first-page":"3","volume-title":"The rat nervous system","author":"Scremin O. U.","year":"1995"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.193631"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.06.016"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.10.038"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.116"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.12396"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb1000422"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2007.12.009"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi8343"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0149-06.2006"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112935"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.08.015"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-019-01045-7"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10217"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.12.007"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.615998"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.71832"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.8178","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T08:47:01Z","timestamp":1718182021000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.8178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,15]]},"references-count":64,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/ptr.8178"],"URL":"https:\/\/doi.org\/10.1002\/ptr.8178","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,15]]},"assertion":[{"value":"2023-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}