Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension
Xiang-Yu Ji,1– 3 Cheng-Jing Lei,2,3 Shuang Kong,2,3 Han-Fei Li,2,3 Si-Yu Pan,2,3 Yu-Jing Chen,2,3 Fan-Rong Zhao,2,3 Tian-Tian Zhu1– 3 1Department of Pharmacy, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2College of Pharmacy, Xinxiang Med...
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Dove Medical Press
2024-02-01
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author | Ji XY Lei CJ Kong S Li HF Pan SY Chen YJ Zhao FR Zhu TT |
author_facet | Ji XY Lei CJ Kong S Li HF Pan SY Chen YJ Zhao FR Zhu TT |
author_sort | Ji XY |
collection | DOAJ |
description | Xiang-Yu Ji,1– 3 Cheng-Jing Lei,2,3 Shuang Kong,2,3 Han-Fei Li,2,3 Si-Yu Pan,2,3 Yu-Jing Chen,2,3 Fan-Rong Zhao,2,3 Tian-Tian Zhu1– 3 1Department of Pharmacy, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, Henan, People’s Republic of ChinaCorrespondence: Tian-Tian Zhu, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China, Tel +86 15225990135, Email zhutt@xxmu.edu.cnPurpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA.Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology.Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1.Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.Keywords: network pharmacology, molecular docking, hydroxy-safflower yellow A, pulmonary arterial hypertension |
first_indexed | 2024-03-07T23:29:41Z |
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language | English |
last_indexed | 2024-03-07T23:29:41Z |
publishDate | 2024-02-01 |
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series | Drug Design, Development and Therapy |
spelling | doaj.art-721c776dc2c54248b1e58484c1fa0e042024-02-20T17:10:12ZengDove Medical PressDrug Design, Development and Therapy1177-88812024-02-01Volume 1847549190587Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial HypertensionJi XYLei CJKong SLi HFPan SYChen YJZhao FRZhu TTXiang-Yu Ji,1– 3 Cheng-Jing Lei,2,3 Shuang Kong,2,3 Han-Fei Li,2,3 Si-Yu Pan,2,3 Yu-Jing Chen,2,3 Fan-Rong Zhao,2,3 Tian-Tian Zhu1– 3 1Department of Pharmacy, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, Henan, People’s Republic of ChinaCorrespondence: Tian-Tian Zhu, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, 453003, People’s Republic of China, Tel +86 15225990135, Email zhutt@xxmu.edu.cnPurpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA.Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology.Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1.Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.Keywords: network pharmacology, molecular docking, hydroxy-safflower yellow A, pulmonary arterial hypertensionhttps://www.dovepress.com/hydroxy-safflower-yellow-a-mitigates-vascular-remodeling-in-rat-pulmon-peer-reviewed-fulltext-article-DDDTnetwork pharmacologymolecular dockinghydroxy-safflower yellow apulmonary arterial hypertension |
spellingShingle | Ji XY Lei CJ Kong S Li HF Pan SY Chen YJ Zhao FR Zhu TT Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension Drug Design, Development and Therapy network pharmacology molecular docking hydroxy-safflower yellow a pulmonary arterial hypertension |
title | Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension |
title_full | Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension |
title_fullStr | Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension |
title_full_unstemmed | Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension |
title_short | Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension |
title_sort | hydroxy safflower yellow a mitigates vascular remodeling in rat pulmonary arterial hypertension |
topic | network pharmacology molecular docking hydroxy-safflower yellow a pulmonary arterial hypertension |
url | https://www.dovepress.com/hydroxy-safflower-yellow-a-mitigates-vascular-remodeling-in-rat-pulmon-peer-reviewed-fulltext-article-DDDT |
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