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Abstract
Purpose
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.
Data Sharing Statement
The authors confirm that the data supporting the findings of this study are available within the article.
Acknowledgments
This project was supported by funding from the National Natural Science Foundation of China (81800051, 82300073), Key Scientific Research Projects of Henan Province (22A180010), Henan Province science and technology research project (212102310319), Key scientific research project of Henan University (22A180010), Research Foundation of Xinxiang Medical University (XYBSKYZZ202108), and the Provincial College Students Innovation and Entrepreneurship Training Program of Xinxiang Medical University (202310472017).
Author Contributions
The author played a substantial role in the review, whether in the conception, design, or all of these aspects, agreed on the journal to which the article has been submitted, reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage, and agreed to take responsibility and be accountable for the contents of the article.
Fan-Rong Zhao: substantially revised or critically reviewed the article; Xiang-Yu Ji: execution and written the article; Cheng-Jing Lei: execution, acquisition of data, analysis and interpretation; Shuang Kong, Han-Fei Li, and Si-Yu Pan: acquisition of data, analysis and interpretation; Yu-Jing Chen: substantially revised or critically reviewed the article; Tian-Tian Zhu: conception, study design.
Disclosure
The authors report no conflicts of interest in this work.