Flavonoid-like Components of Peanut Stem and Leaf Extract Promote Sleep by Decreasing Neuronal Excitability.

Scope Peanut stem and leaf (PSL), a traditional Chinese medicine, is widely used as a dietary supplement to improve sleep quality, however, the underlying mechanism is unclear. Here, we aimed to determine whether active compounds in PSL extract exert their effects by mediating neuronal excitability. Methods and results Aqueous PSL extract (500 mg/kg BW) increased the duration of total sleep (TS), slow wave sleep (SWS) and rapid eye movement sleep (REMS) in BALB/c mice after 7 and 14 continuous days of intragastric administration. Two PSL extract components with flavonoid-like structures: 4',7-di-O-methylnaringenin (DMN, 61 μg/kg BW) and 2'-O-methylisoliquiritigenin (MIL, 12 μg/kg BW), showed similar effects on sleep in BALB/c mice. Moreover, incubation with DMN (50 μM) and MIL (50 μM) acutely reduced voltage-gated sodium and potassium currents and suppressed the firing of evoked action potential in mouse cortical neurons, indicating the inhibition on neuronal excitability. Meanwhile, RNA-seq analysis predicted the potential regulation of voltage-gated channels, which is according with the molecular docking simulation that both MIL and DMN can bind to Nav 1.2. Conclusions DMN and MIL are the active ingredients of PSL that improve sleep quality, suggesting that PSL promotes sleep by regulating the excitability of neurons. This article is protected by copyright. All rights reserved.