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 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 targe