Cargando…

Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Hongfa, Zhang, Yawen, Guo, Xiaoyao, Wang, Xuan, Wang, Hanyu, Zhao, Hui, Wang, Lei, Zou, Haiyan, Zhang, Qiuxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925249/
https://www.ncbi.nlm.nih.gov/pubmed/36793760
http://dx.doi.org/10.1155/2023/8673136
_version_ 1784888024247566336
author Cheng, Hongfa
Zhang, Yawen
Guo, Xiaoyao
Wang, Xuan
Wang, Hanyu
Zhao, Hui
Wang, Lei
Zou, Haiyan
Zhang, Qiuxia
author_facet Cheng, Hongfa
Zhang, Yawen
Guo, Xiaoyao
Wang, Xuan
Wang, Hanyu
Zhao, Hui
Wang, Lei
Zou, Haiyan
Zhang, Qiuxia
author_sort Cheng, Hongfa
collection PubMed
description 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 g/kg (HSHS5.25), and HSHS 10.5 g/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-eosin (HE). The mRNA expression profiles were identified using microarray analysis and quantitative real-time PCR (qRT-PCR) 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-2 ratio and suppressed caspase-3 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-CREB signaling pathway may be a potential mechanism for HSHS in the treatment of ischemic stroke.
format Online
Article
Text
id pubmed-9925249
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-99252492023-02-14 Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification Cheng, Hongfa Zhang, Yawen Guo, Xiaoyao Wang, Xuan Wang, Hanyu Zhao, Hui Wang, Lei Zou, Haiyan Zhang, Qiuxia Evid Based Complement Alternat Med Research Article 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 g/kg (HSHS5.25), and HSHS 10.5 g/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-eosin (HE). The mRNA expression profiles were identified using microarray analysis and quantitative real-time PCR (qRT-PCR) 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-2 ratio and suppressed caspase-3 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-CREB signaling pathway may be a potential mechanism for HSHS in the treatment of ischemic stroke. Hindawi 2023-02-06 /pmc/articles/PMC9925249/ /pubmed/36793760 http://dx.doi.org/10.1155/2023/8673136 Text en Copyright © 2023 Hongfa Cheng et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cheng, Hongfa
Zhang, Yawen
Guo, Xiaoyao
Wang, Xuan
Wang, Hanyu
Zhao, Hui
Wang, Lei
Zou, Haiyan
Zhang, Qiuxia
Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification
title Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification
title_full Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification
title_fullStr Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification
title_full_unstemmed Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification
title_short Study on Neuroprotective Mechanism of Houshiheisan in Ischemic Stroke Based on Transcriptomics and Experimental Verification
title_sort study on neuroprotective mechanism of houshiheisan in ischemic stroke based on transcriptomics and experimental verification
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925249/
https://www.ncbi.nlm.nih.gov/pubmed/36793760
http://dx.doi.org/10.1155/2023/8673136
work_keys_str_mv AT chenghongfa studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT zhangyawen studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT guoxiaoyao studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT wangxuan studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT wanghanyu studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT zhaohui studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT wanglei studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT zouhaiyan studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification
AT zhangqiuxia studyonneuroprotectivemechanismofhoushiheisaninischemicstrokebasedontranscriptomicsandexperimentalverification