The modulatory effects of persimmon leaf extract on sleep-related neurotransmitters and its potential hypnotic effects.

Purpose: Persimmon leaf is a traditional herbal medicine with diverse therapeutic applications. This study aimed to explore the effect of persimmon leaf extract (PLE) on the modulation of neurotransmitters involved in sleep regulation and its overall impact on sleep latency and duration.

Methods: The key components of PLE were identified by ultra performance liquid chromatography. The modulatory effects of PLE in sleep and wakefulness-related neurotransmitters were studied in human neuroblastoma SH-SY5Y cells. PLE was also investigated in pentobarbital sodium-induced sleep and para-chlorophenylalanine (PCPA)-induced insomnia models in mice and rats.

Results: PLE induced chloride influx and increased the intracellular production of gamma-aminobutyric acid (GABA), a neurotransmitter crucial for sleep regulation, in SH-SY5Y cells. Furthermore, PLE influenced the cellular expressions of serotonin, dopamine, and adenosine. It increased monoamine oxidase enzyme-A activity and reduced serotonin levels and its metabolites. It induced dopamine biosynthesis and degradation pathways. In the pentobarbital-induced sleep experiment, PLE significantly prolonged total sleep duration and reduced sleep latency in a dose-dependent manner. In the PCPA-induced insomnia model, PLE consistently increased GABA production, and lowered dopamine expression.

Conclusion: PLE exhibited modulatory effects on sleep-related neurotransmitters in vitro, which may also contribute to its hypnotic effects by extending the sleep duration and shortening sleeping latency in vivo.