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...

Full description

Bibliographic Details
Main Authors: Ji XY, Lei CJ, Kong S, Li HF, Pan SY, Chen YJ, Zhao FR, Zhu TT
Format: Article
Language:English
Published: Dove Medical Press 2024-02-01
Series:Drug Design, Development and Therapy
Subjects:
Online Access:https://www.dovepress.com/hydroxy-safflower-yellow-a-mitigates-vascular-remodeling-in-rat-pulmon-peer-reviewed-fulltext-article-DDDT
_version_ 1797301933368672256
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
format Article
id doaj.art-721c776dc2c54248b1e58484c1fa0e04
institution Directory Open Access Journal
issn 1177-8881
language English
last_indexed 2024-03-07T23:29:41Z
publishDate 2024-02-01
publisher Dove Medical Press
record_format Article
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
work_keys_str_mv AT jixy hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension
AT leicj hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension
AT kongs hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension
AT lihf hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension
AT pansy hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension
AT chenyj hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension
AT zhaofr hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension
AT zhutt hydroxysaffloweryellowamitigatesvascularremodelinginratpulmonaryarterialhypertension