Unveiling the Therapeutic Mechanisms of Chinese Herbs in Heart Failure: Integrating Network Pharmacology, Molecular Docking, and Simulation Analysis.

Background: Heart failure (HF) is a leading cause of mortality and represents the final stage of various cardiovascular disorders. Although traditional Chinese herbs have been extensively applied in HF treatment and their clinical efficacy has been investigated, the underlying molecular mechanisms remain insufficiently understood. To address this gap, systematic approaches are required to elucidate the therapeutic basis of herbal interventions. Methods: In this study, we systematically analyzed the bioactive compounds from seven traditional Chinese herbs, Baiguo (Ginkgo biloba), Chishao (Radix Paeoniae Rubra), Biba (Piper longum), Aidicha (Ilex latifolia), Bajiaolian (Dysosma spp.), Beiwuweizi (Schisandra chinensis), and Baiqucai (Sedum sarmentosum) and explored their potential mechanisms in HF by integrating network pharmacology, molecular docking, and molecular dynamics simulations. Result: We identified key targets and pathways implicated in HF pathogenesis and herbal interventions. A total of 63 active compounds were found to regulate 1947 genes. Through integrative analysis of the GSE57338 heart failure dataset from the GEO database, we further identified 265 intersecting targets shared between herb-associated genes and HF-related genes, highlighting their potential involvement in HF progression. Network analysis prioritized three hub proteins, STAT3, SRC, and TP53, which were subsequently subjected to molecular docking with the top bioactive compounds (quercetin, kaempferol, and epigallocatechin-3-gallate). Docking studies revealed strong binding affinities, and molecular dynamics (MD) simulations further validated the stability of these protein compound interactions. Conclusions: This study elucidates key bioactive components and targets involved in HF treatment, with kaempferol and epigallocatechin-3-gallate emerging as promising therapeutic candidates. These results provide a foundation for future experimental validation and the development of targeted HF therapies derived from traditional Chinese medicine.