Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension

• Published in: Drug design, development and therapy Vol. 18; pp. 475 - 491
• Main Authors: Ji, Xiang-Yu, Lei, Cheng-Jing, Kong, Shuang, Li, Han-Fei, Pan, Si-Yu, Chen, Yu-Jing, Zhao, Fan-Rong, Zhu, Tian-Tian
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2024; Dove Medical Press
• Subjects: Animals; Chalcone - analogs & derivatives; Chalcone - pharmacology; Drugs, Chinese Herbal; Health aspects; Humans; Hydrogen; hydroxy-safflower yellow a; Medical research; Medicine, Experimental; molecular docking; Molecular Docking Simulation; network pharmacology; Protein-protein interactions; pulmonary arterial hypertension; Pulmonary Arterial Hypertension - chemically induced; Pulmonary Arterial Hypertension - drug therapy; Pulmonary hypertension; Quinones; Rats; Vascular Remodeling; China; hydroxy-safflower yellow A; molecular docking; network pharmacology; pulmonary arterial hypertension
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S439686

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. 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. 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. 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.