Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis
Hydroxysafflor yellow A (HSYA) is derived from <i>Carthamus tinctorius</i> L. (Honghua in Chinese) and is used to treat cardiovascular and cerebrovascular disease. However, the mechanism by which HSYA treats ischemic stroke following atherosclerosis (ISFA) remains unclear. The targets an...
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MDPI AG
2023-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/23/7829 |
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| author | Xi Han Huifen Zhou Junjun Yin Jiaqi Zhu Jiehong Yang Haitong Wan |
| author_facet | Xi Han Huifen Zhou Junjun Yin Jiaqi Zhu Jiehong Yang Haitong Wan |
| author_sort | Xi Han |
| collection | DOAJ |
| description | Hydroxysafflor yellow A (HSYA) is derived from <i>Carthamus tinctorius</i> L. (Honghua in Chinese) and is used to treat cardiovascular and cerebrovascular disease. However, the mechanism by which HSYA treats ischemic stroke following atherosclerosis (ISFA) remains unclear. The targets and pathways of HSYA against ISFA were obtained using network analysis. A total of 3335 potential IFSA-related targets were predicted using the GenCards and Drugbank databases, and a total of 88 potential HSYA-related targets were predicted using the Swiss Target Prediction database. A total of 62 HSYA-related targets against IFSA were obtained. The network was composed of HSYA, 62 targets, and 20 pathways. The top 20 targets were constructed via the protein–protein interaction (PPI) network. Gene Ontology analysis revealed that the targets were involved in signal transduction, protein phosphorylation, the cytoplasm, the plasma membrane, the cytosol, zinc ion binding, ATP binding, protein kinase binding/activity, and enzyme binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the pathways were associated with cancer, inflammatory mediator regulation of the transient receptor potential channels, and microRNA in cancer. Additionally, molecular docking indicated that HSYA mainly interacts with five targets, namely interleukin 1 beta (IL-1β), signal transducer and activator of transcription 3 (STAT3), E1A-binding protein p300 (EP300), protein kinase C alpha (PRKCA), and inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB). In animal experiments, HSYA administration ameliorated the infarct size, neurological deficit score, histopathological changes, carotid intima-media thickness (IMT), and blood lipid level (total cholesterol and triglycerides). Immunochemistry and quantitative PCR showed that HSYA intervention downregulated the expression of STAT3, EP300, PRKCA, and IKBKB, and the enzyme-linked immunoassay showed reduced IL-1β levels. The findings of this study provide a reference for the development of anti-ISFA drugs. |
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| language | English |
| last_indexed | 2024-03-09T01:45:36Z |
| publishDate | 2023-11-01 |
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| series | Molecules |
| spelling | doaj.art-06cc0ded630e473680b4acd5e8bc117f2023-12-08T15:22:28ZengMDPI AGMolecules1420-30492023-11-012823782910.3390/molecules28237829Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following AtherosclerosisXi Han0Huifen Zhou1Junjun Yin2Jiaqi Zhu3Jiehong Yang4Haitong Wan5School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaHydroxysafflor yellow A (HSYA) is derived from <i>Carthamus tinctorius</i> L. (Honghua in Chinese) and is used to treat cardiovascular and cerebrovascular disease. However, the mechanism by which HSYA treats ischemic stroke following atherosclerosis (ISFA) remains unclear. The targets and pathways of HSYA against ISFA were obtained using network analysis. A total of 3335 potential IFSA-related targets were predicted using the GenCards and Drugbank databases, and a total of 88 potential HSYA-related targets were predicted using the Swiss Target Prediction database. A total of 62 HSYA-related targets against IFSA were obtained. The network was composed of HSYA, 62 targets, and 20 pathways. The top 20 targets were constructed via the protein–protein interaction (PPI) network. Gene Ontology analysis revealed that the targets were involved in signal transduction, protein phosphorylation, the cytoplasm, the plasma membrane, the cytosol, zinc ion binding, ATP binding, protein kinase binding/activity, and enzyme binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the pathways were associated with cancer, inflammatory mediator regulation of the transient receptor potential channels, and microRNA in cancer. Additionally, molecular docking indicated that HSYA mainly interacts with five targets, namely interleukin 1 beta (IL-1β), signal transducer and activator of transcription 3 (STAT3), E1A-binding protein p300 (EP300), protein kinase C alpha (PRKCA), and inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB). In animal experiments, HSYA administration ameliorated the infarct size, neurological deficit score, histopathological changes, carotid intima-media thickness (IMT), and blood lipid level (total cholesterol and triglycerides). Immunochemistry and quantitative PCR showed that HSYA intervention downregulated the expression of STAT3, EP300, PRKCA, and IKBKB, and the enzyme-linked immunoassay showed reduced IL-1β levels. The findings of this study provide a reference for the development of anti-ISFA drugs.https://www.mdpi.com/1420-3049/28/23/7829hydroxysafflor yellow Aischemia stroke following atherosclerosisnetwork analysisanimal experiments |
| spellingShingle | Xi Han Huifen Zhou Junjun Yin Jiaqi Zhu Jiehong Yang Haitong Wan Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis Molecules hydroxysafflor yellow A ischemia stroke following atherosclerosis network analysis animal experiments |
| title | Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis |
| title_full | Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis |
| title_fullStr | Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis |
| title_full_unstemmed | Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis |
| title_short | Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis |
| title_sort | network analysis and experimental verification of the mechanisms of hydroxysafflor yellow a in ischemic stroke following atherosclerosis |
| topic | hydroxysafflor yellow A ischemia stroke following atherosclerosis network analysis animal experiments |
| url | https://www.mdpi.com/1420-3049/28/23/7829 |
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