Migration Characteristics and Mechanism of Active Components From Jieyu Anshen Granule in Different Insomnia Mouse Models

RATIONALE: Insomnia is a highly prevalent disorder with substantial health and socioeconomic impacts, for which traditional Chinese medicine is an important treatment option. Jieyu Anshen Granule (JYAS-G) shows excellent clinical efficacy in insomnia treatment, but its active components, in vivo migration characteristics and underlying mechanisms remain unclear. METHODS: Two mouse insomnia models induced by p-chlorophenylalanine (PCPA, chemical method) and sleep deprivation machine (SDM, physical method) were established respectively, and mice were administered with low and high doses of JYAS-G, with open field test used to evaluate the pharmacodynamic effects. UHPLC-Q-Orbitrap-MS combined with GNPS was applied to systematically identify the in vitro components of JYAS-G and its migration profiles in mouse plasma, liver, heart, prefrontal cortex, hippocampus, and hypothalamus. RESULTS: The SDM model induced insomnia with manic-like behaviors, which were significantly ameliorated by JYAS-G, whereas the PCPA model produced no significant insomnia-like phenotypes under the current conditions. In total, 89 in vitro components and 43 blood-absorbed components of JYAS-G were identified, showing marked tissue-specific distribution. Network pharmacology and molecular docking identified core components, including furanogermenone and curcumenol, predicted to exert anti-insomnia effects by targeting ADORA2A, GABRB3, and SLC6A4 and regulating the neuroactive ligand-receptor interaction pathway. CONCLUSIONS: This study characterizes the in vivo migration characteristics of JYAS-G and provides insights into its multi-target anti-insomnia mechanism, while comparing the modeling differences between two common insomnia animal models. These findings provide scientific evidence for the rational clinical application and further development of JYAS-G.