Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective.

Abstract

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein-protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.