{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:20:03Z","timestamp":1789014003148,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873224"],"award-info":[{"award-number":["81873224"]}],"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":["81373526"],"award-info":[{"award-number":["81373526"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has shown outstanding efficacy in treating stroke. This study investigated various therapeutic targets of HSHS for ischemic stroke using mRNA transcriptomics. Herein, rats were randomly separated into the sham, model, HSHS 5.25\u2009g\/kg (HSHS5.25), and HSHS 10.5\u2009g\/kg (HSHS10.5) groups. Rats suffering from stroke were induced by permanent middle cerebral artery occlusion (pMCAO). After seven days of HSHS treatment, behavioral tests were conducted, and histological damage was examined with hematoxylin\u2010eosin (HE). The mRNA expression profiles were identified using microarray analysis and quantitative real\u2010time PCR (qRT\u2010PCR) validated gene expression changes. An analysis of gene ontology and pathway enrichment was conducted to analyze potential mechanisms confirmed using immunofluorescence and western blotting. HSHS5.25 and HSHS10.5 improved neurological deficits and pathological injury in pMCAO rats. The intersections of 666 differentially expressed genes (DEGs) were chosen using transcriptomics analysis in the sham, model, and HSHS10.5 groups. The enrichment analysis suggested that the therapeutic targets of HSHS might regulate the apoptotic process and ERK1\/2 signaling pathway, which was related to neuronal survival. Moreover, TUNEL and immunofluorescence analysis indicated that HSHS inhibited apoptosis and enhanced neuronal survival in the ischemic lesion. Western blot and immunofluorescence assay indicated that HSHS10.5 decreased Bax\/Bcl\u20102 ratio and suppressed caspase\u20103 activation, while the phosphorylation of ERK1\/2 and CREB was upregulated in a stroke rat model after HSHS treatment. Effective inhibition of neuronal apoptosis by activating the ERK1\/2\u2010CREB signaling pathway may be a potential mechanism for HSHS in the treatment of ischemic stroke.<\/jats:p>","DOI":"10.1155\/2023\/8673136","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T20:20:06Z","timestamp":1675714806000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification"],"prefix":"10.1155","volume":"2023","author":[{"given":"Hongfa","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5331-0318","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-5699","authenticated-orcid":false,"given":"Qiuxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000558"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30500-3"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319948"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.039287"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg-2018-013911"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD010820.pub2"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2021.5070"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2014.11.002"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8868941"},{"key":"e_1_2_10_10_2","first-page":"140","article-title":"Hou\u2019s heisan combined with western medicine in treating acute ischemic stroke for 45 cases","volume":"13","author":"Cai Z.","year":"2015","journal-title":"Chinese Medicine Modern Distance Education of China"},{"key":"e_1_2_10_11_2","article-title":"Clinicle obeservation on the treatment of warming yang calming the wind and resolving phlegm in the therapy of spasticity for stroke patients","volume":"8","author":"Sun X.","year":"2010","journal-title":"Chinese Journal of Integrative Medicine on Cardio\/Cerebrovascular Disease"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1673-5374.2012.24.002"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.131580"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.235031"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20191006"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbt063"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112057"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12531"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12550"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.15.91"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01570"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.900128"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-021-00431-4"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.11.005"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.1.84"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2012.07.009"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab447"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjacc\/zuac004"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.963179"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570161115666161104095522"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-2236(99)01401-0"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.531632"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-019-01556-6"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1080\/02699050500284218"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290105"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.3109\/10799893.2015.1030412"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-006-0106-x"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2016.04.007"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00046"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26960"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00421"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.69892"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.01836.x"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(99)01500-3"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600024"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2023\/8673136.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2023\/8673136.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2023\/8673136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T15:29:26Z","timestamp":1722958166000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2023\/8673136"}},"subtitle":[],"editor":[{"given":"Talha Bin","family":"Emran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1155\/2023\/8673136"],"URL":"https:\/\/doi.org\/10.1155\/2023\/8673136","archive":["Portico"],"relation":{},"ISSN":["1741-427X","1741-4288"],"issn-type":[{"value":"1741-427X","type":"print"},{"value":"1741-4288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"2022-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"8673136"}}