Evaluating the Therapeutic Role of Selected Active Compounds in Plumula Nelumbinis on Pulmonary Hypertension via Network Pharmacology and Experimental Analysis

Abstract

Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the most critical factors leading to vascular remodeling in pulmonary hypertension (PH). This study aimed to explore the effect and potential mechanism of Plumula Nelumbinis on PH by using network pharmacology and experimental analysis. The potential active components of Plumula Nelumbinis and their targets were obtained from TCMSP and PharmMapper databases. The PH-related targets were obtained from GeneCards, OMIM, DisGeNET, and TTD databases. Co-targets between Plumula Nelumbinis and PH were obtained by drawing Venn diagrams. The protein-protein interaction networks and compound-target-pathway networks were established using the STRING database and Cytoscape software. Moreover, the binding activities of core targets and essential active compounds were further validated by molecular docking. Finally, we further confirmed in vitro experiments that the main active components of Plumula Nelumbinis could inhibit the proliferation of PASMCs induced by hypoxia, as well as the increased expression of p-SRC and PIM1. Based on these observations, we conclude that multi-components (neferine, liensinine, and isoliensinine) in Plumula Nelumbinis can inhibit the hypoxia-induced proliferation of PASMCs by regulating the expression of p-SRC and PIM1, thereby delaying the development of PH.