Flavonoid‐Like Components of Peanut Stem and Leaf Extract Promote Sleep by Decreasing Neuronal Excitability

Abstract

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, the study aims to determine whether active compounds in PSL extract exert their effects by mediating neuronal excitability. Methods and Results: Aqueous PSL extract (500 mg kg −1 BW) increases 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 −1 BW) and 2'-O-methylisoliquiritigenin (MIL, 12 µg kg −1 BW), show similar effects on sleep in BALB/c mice. Moreover, incubation with DMN (50 µM) and MIL (50 µM) acutely reduces voltage-gated sodium and potassium currents and suppresses the firing of evoked action potential in mouse cortical neurons, indicating the inhibition on neuronal excitability. Meanwhile, RNA-seq analysis predicts the potential regulation of voltage-gated channels, which is according with the molecular docking simulation that both MIL and DMN can bind to voltage gated sodium channels 1.2 (Na v 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.

Dietary Intake of Flavonoids Associated with Sleep Problems: An Analysis of Data from the National Health and Nutrition Examination Survey, 2007–2010

“…Flavonoids’ exceptional biological activities and nutritional properties sparked our interest in exploring their pharmacological effects on sleep. It has been demonstrated that flavonoid therapy could improve sleep problems by having fewer negative effects [ 15 ], which makes us wonder whether flavonoid intakes are also connected with sleep duration and sleep disorders.…”

“…Compared with traditional pharmacotherapy including tranquilizers and hypnotics, herbal medicines have fewer side effects. The flavonoids extracted from the stems and leaves of peanuts could reduce neuronal excitability to improve sleep quality [ 15 ]. There were few studies on the relationship between isoflavone intake and sleep.…”

(−)-Naringenin 4′,7-dimethyl Ether Isolated from Nardostachys jatamansi Relieves Pain through Inhibition of Multiple Channels

“…As an enantiomer, NRG-DM extracted from peanut stem and leaf promoted sleep by dampening neuronal excitability. In cortical neurons, the inhibitory activity of NRG-DM on Nav channels appeared to be more potent than that on Kv channels [ 51 ]. However, in the current study, due to the higher IC 50 value, our data showed that inhibition of Nav channels might contribute to (−)-NRG-DM-produced analgesic activity but the effect is secondary to that of Kv channels.…”

Clinical efficacy of Luohua Anshen oral liquid in the treatment of short-term insomnia disorders (syndrome of depressed liver qi transforming into fire): protocol for a single-center, double-blinded, randomized, placebo-controlled trial

“…These include serine, hippuric acid, indole 3 propionic acid, butanediol and cytosine. Serine can promote awakening [14], and the concentration of serine can be reduced after intervention with Luohua Anshen Oral Liquid. Luohua Anshen Oral liquid has been clinically to treat insomnia more than 100,000 times, and more than 1,200 cases have been identi ed in scienti c research [12].…”