Exploration of Potential Pharmacodynamic Components and Mechanisms of Yishen Ningxin Formula for Hypertension Comorbid Insomnia via UPLC‐QE‐MS and Network Pharmacology

This study investigated the chemical profile and therapeutic mechanisms of the Yishen Ningxin Formula (YSNXF) in treating hypertension comorbid with insomnia through an integrated approach involving UPLC-QE-MS/MS, network pharmacology, and molecular docking. Chemical profiling identified a total of 870 components within YSNXF, with 13 compounds confirmed as blood-entering components in rat plasma, corresponding to 133 potential targets. Intersection analysis with disease-related targets revealed 46 core targets, notably ACE, HTR2A, HTR2B, and HTR1A. Network pharmacology and enrichment analyses indicated that key bioactive components-including hirsutine, geissoschizine methyl ether, hypaphorine, and N-acetylleucine-exert their effects via critical pathways such as the renin-angiotensin system, neuroactive ligand-receptor interactions, and serotonergic synapses. Molecular docking further validated the strong binding affinities of geissoschizine methyl ether and hypaphorine to the identified core targets. These findings suggest that YSNXF alleviates hypertension and insomnia through a multi-component, multi-target, and multi-pathway synergistic mechanism, highlighting geissoschizine methyl ether and hypaphorine as pivotal active constituents for further pharmacological validation.