Mechanism of action of aloperine in the treatment of pulmonary arterial hypertension based on network pharmacology and molecular docking methods.

Abstract

Background: Pulmonary arterial hypertension is a severe pulmonary vascular disease, marked by high mortality and substantial treatment costs, underscoring the urgent need for the exploration of traditional Chinese medicine as a potential therapeutic strategy for pulmonary hypertension. This study aimed to investigate the underlying mechanisms of aloperine in treating PAH through network pharmacology and molecular docking approaches.

Methods: The Swiss Target Prediction database was employed to predict molecular targets of aloperine, while Cytoscape was used to construct the "active component-target" network. Disease-associated targets were identified through the GeneCards and OMIM databases and cross-referenced with drug targets to determine effective targets of aloperine for PAH treatment. Analysis of protein-protein interaction (PPI) was conducted using the STRING database. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out via the Metascape platform.

Results: Following screening, 42 molecular targets of aloperine, 1264 disease-related targets, and 23 effective targets of aloperine in treating PAH were identified. The PPI analysis revealed that aloperine targets SLC6A2, ADRA1B, CYP2D6, CCR5, and JAK2, all of which play a therapeutic role in PAH. The GO and KEGG pathway analyses identified relevant biological functions, such as membrane raft organization, G protein-coupled amine receptor activity, and regulation of tube diameter, as well as ten pathways including neuroactive ligand-receptor interaction, the cGMP-PKG signaling pathway, calcium signaling, and vascular smooth muscle contraction. Molecular docking results confirmed the interaction between aloperine and its key targets, with a high docking affinity observed between aloperine and the core target ADRA1A.

Conclusion: Network pharmacology analysis demonstrated that aloperine exerts its therapeutic effects in PAH primarily through multi-target and multi-pathway mechanisms, providing a novel direction and foundation for PAH treatment.