Unraveling the Mechanism of Higenamine in the Treatment of Right Heart Failure via Computational Drug Discovery and Molecular Simulation Technology

Right heart failure (RHF) represents a multifactorial and clinically challenging syndrome characterized by complex pathophysiology and a persistent unmet therapeutic need. Despite an extensive body of literature delineating diverse putative determinants capable of modulating disease susceptibility and progression, the precise molecular mechanisms continue to be inadequately elucidated. The purpose of this study was to identify mechanisms underlying higenamine (HIG)-mediated therapy for RHF by combining network pharmacology with molecular dynamics (MD) techniques. Based on drug-likeness properties, HIG was identified as a promising phytoconstituent against RHF. It is predicted to exert its effects by modulating pathways related to pro-growth, angiogenesis and inflammation, all of which are associated with ESR1, PPARG and TGFBR1. Molecular docking and MD were subsequently employed to further confirm the binding of HIG to ESR1. Finally, HIG is considered to hold potential in modulating key pathological pathways of RHF, offering a promising experimental basis for the future development of novel therapeutics against RHF.