Prunella vulgaris Compound Improves Sleep Architecture and Attenuates Hippocampal Injury in Insomnia Mice

Insomnia is associated with disrupted sleep architecture, hippocampal pathological alterations, neurotransmitter imbalance, and neuroinflammatory responses. This study evaluated the effects of the Prunella vulgaris compound (PVC) on sleep architecture and hippocampal alterations in p-chlorophenylalanine (PCPA)-induced insomnia model mice and examined their association with NLRP3-related pyroptotic signaling. PVC was characterized using UPLC-Q-Exactive Orbitrap MS and targeted HPLC quantification. PCPA-induced insomnia models were established in ICR and C57BL/6N mice for pharmacodynamic and molecular assessments and EEG/EMG recording, respectively. Sleep outcomes were assessed using the pentobarbital-induced sleep test and EEG/EMG; hippocampal histomorphology, neurotransmitters, and inflammasome- and pyroptosis-related markers were evaluated using histological, biochemical, RT-qPCR, and Western blot analyses. UPLC-MS tentatively characterized 198 constituents, and salviaflaside, rosmarinic acid, and linarin were quantified by HPLC. PVC shortened sleep latency, prolonged sleep duration, reduced wakefulness, increased NREM and REM sleep, and improved sleep continuity. It also attenuated hippocampal histomorphological alterations; modulated 5-HT, GABA, glutamate, and dopamine levels; and reduced NLRP3 inflammasome- and pyroptosis-related markers together with IL-1β and IL-18. PVC improved insomnia-like phenotypes and attenuated hippocampal pathological alterations in PCPA-induced insomnia model mice. These effects were associated with improved sleep architecture and neurotransmitter homeostasis and with reduced NLRP3/caspase-1/GSDMD-related signaling.