Shenfu Injection attenuates isoproterenol-induced heart failure partly through modulation of the TNF-α/TNFR1/NF-κB signaling pathway

Shenfu injection (SFI) is widely used for heart failure (HF), but its cardioprotective mechanism remains incompletely understood. In this study, an isoproterenol-induced HF rat model, H9c2 cell injury model, network pharmacology, GEO analysis, molecular docking, and molecular dynamics simulations were integrated to explore the mechanism of SFI. In rats, SFI improved cardiac function, with the medium-dose group increasing LVEF from 62.03 ± 5.89% in the ISO group to 79.33 ± 2.62% and LVFS from 29.68 ± 3.97% to 43.03 ± 2.49%. SFI also reduced NT-proBNP, inflammatory cytokines, and myocardial apoptosis. In H9c2 cells, 4‰ SFI improved ISO-induced cell injury and reduced apoptosis and inflammatory responses. Network pharmacology and GEO analysis indicated enrichment of the TNF signaling pathway, and molecular simulation suggested potential interactions between candidate SFI-related compounds and targets in the TNF-α/TNFR1/NF-κB axis. These findings suggest that SFI attenuates HF-related cardiac injury partly by suppressing inflammation and apoptosis through modulation of the TNF-α/TNFR1/NF-κB signaling pathway.