Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction

Abstract Subarachnoid hemorrhage (SAH) is a fatal pathological condition in the central nervous system (CNS), characterized by severe clinical consequences. Its treatment remains a significant challenge, especially due to the incomplete understanding of its molecular mechanisms. In this study, we in...

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Main Authors: Yi Liu, Yang Zhang, Huan Wei, Li Wang, Lishang Liao
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97642-8
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author Yi Liu
Yang Zhang
Huan Wei
Li Wang
Lishang Liao
author_facet Yi Liu
Yang Zhang
Huan Wei
Li Wang
Lishang Liao
author_sort Yi Liu
collection DOAJ
description Abstract Subarachnoid hemorrhage (SAH) is a fatal pathological condition in the central nervous system (CNS), characterized by severe clinical consequences. Its treatment remains a significant challenge, especially due to the incomplete understanding of its molecular mechanisms. In this study, we integrated comprehensive bioinformatics analyses with experimental validation to explore the potential pathogenic mechanisms and immune cell infiltration characteristics of SAH, aiming to identify novel diagnostic biomarkers and therapeutic targets. We selected relevant gene expression data from the gene expression omnibus (GEO) database and obtained a gene set associated with SAH from the GeneCards database. Through bioinformatics analysis, we constructed a protein-protein interaction (PPI) network and performed functional enrichment analysis using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. The analysis revealed 11 key genes and indicated 3 main signaling pathways. Additionally, Drug target prediction and molecular docking analyses revealed that Isorhynchophylline (IRN) exhibits a strong binding affinity to these hub proteins. Importantly, Western blot (WB) experiments confirmed that IRN significantly downregulates the expression of CCL20, IL6, TLR4, and MMP9 in LPS-induced microglial cells, validating its anti-inflammatory effects. In conclusion, our findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.
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spelling doaj-art-1f2dd1c8a7294398afdefd80df614b282025-08-20T03:18:38ZengNature PortfolioScientific Reports2045-23222025-04-0115111610.1038/s41598-025-97642-8Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug predictionYi Liu0Yang Zhang1Huan Wei2Li Wang3Lishang Liao4Department of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAbstract Subarachnoid hemorrhage (SAH) is a fatal pathological condition in the central nervous system (CNS), characterized by severe clinical consequences. Its treatment remains a significant challenge, especially due to the incomplete understanding of its molecular mechanisms. In this study, we integrated comprehensive bioinformatics analyses with experimental validation to explore the potential pathogenic mechanisms and immune cell infiltration characteristics of SAH, aiming to identify novel diagnostic biomarkers and therapeutic targets. We selected relevant gene expression data from the gene expression omnibus (GEO) database and obtained a gene set associated with SAH from the GeneCards database. Through bioinformatics analysis, we constructed a protein-protein interaction (PPI) network and performed functional enrichment analysis using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. The analysis revealed 11 key genes and indicated 3 main signaling pathways. Additionally, Drug target prediction and molecular docking analyses revealed that Isorhynchophylline (IRN) exhibits a strong binding affinity to these hub proteins. Importantly, Western blot (WB) experiments confirmed that IRN significantly downregulates the expression of CCL20, IL6, TLR4, and MMP9 in LPS-induced microglial cells, validating its anti-inflammatory effects. In conclusion, our findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.https://doi.org/10.1038/s41598-025-97642-8Subarachnoid hemorrhageMolecular mechanismsBioinformaticsDrug predictionIsorhynchophylline
spellingShingle Yi Liu
Yang Zhang
Huan Wei
Li Wang
Lishang Liao
Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction
Scientific Reports
Subarachnoid hemorrhage
Molecular mechanisms
Bioinformatics
Drug prediction
Isorhynchophylline
title Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction
title_full Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction
title_fullStr Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction
title_full_unstemmed Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction
title_short Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction
title_sort exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets insights from bioinformatics and drug prediction
topic Subarachnoid hemorrhage
Molecular mechanisms
Bioinformatics
Drug prediction
Isorhynchophylline
url https://doi.org/10.1038/s41598-025-97642-8
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