Chinese scientist, writing in the Journal Molecular Nutrition and Food Research, make a case for the traditional Chinese medicine’s use as a dietary supplement in improving sleep duration and quality.
The team point to the extract’s ability to prolong the duration of total sleep (TS), slow wave sleep (SWS) and rapid eye movement sleep (REMS).
The researchers, from Beijing’s Chinese Academy of Agricultural Science and also Wageningen University and Research, point to the extract’s effect of reducing sodium (Na) and potassium (K) flow in neuronal cells.
The effect is also accompanied by a suppression of neuronal excitability via increasing the neuronal action potential threshold.
“The current study suggests a novel and convincing link between neuronal excitability and flavonoids with sedative function,” the team states.
“These results confirm that 7-di-O-methylnaringenin (DMN) and 2’-O-methylisoliquiritigenin (MIL) may be the main active components in peanut stem and leaf (PSL) extract, which can significantly improve sleep by regulating the Na and K channels and excitability of neurons.”
DMN and MIL
DMN, a derivative of dihydroflavone and MIL, a free chalconeglycogen, were according to the team, flavonoids that did not show up in a literature search for all flavonoids with ion channels-regulating effects.
The team adds that the experiment findings, “further expand the range of functional flavonoids and suggest a potential approach for the development of sleep-promoting drugs to treat insomnia.”
In the first set of experiments, BALB/c mice were either given saline as the blank control; 125, 250, or 500 milligrams per kilogram body weight (mg kg−1BW) PSL extract; or 5 mg kg−1BW diazepam as a positive control. There were eight rodents per study group.
The concentrations of DMN and MIL in PSL extract were 121.4348 and 24.4093 mg kg−1, respectively.
In the second and third sets of experiments, the team then applied DMN (61 micrograms (μg) per kg−1BW) and MIL (12μg per kg−1BW) at the same concentrations in 500mg kg−1BW PSL extracts on mice.
All drugs were dissolved in sterile saline immediately before use, and intragastrically administered to the mice at 17:00 on the experimental day.
After a 7-day treatment period, EEG and EMG data were recorded for 24 hours following administration of the materials.
The team found aqueous PSL extract (500 mg kg−1BW) increased the duration of TS, SWS and REMS in BALB/c mice after 7 and 14 continuous days of intragastric administration. DMN and MIL showed similar effects on sleep in BALB/c mice.
Additionally, incubation with DMN (50μM) and MIL (50μM) reduced voltage-gated sodium and potassium currents and suppresssd the firing of evoked action potential in mouse cortical neurons,
According to the team, this indicated the inhibition on neuronal excitability.
Simulation models
Meanwhile, RNA-seqanalysis predicted the potential regulation of voltage-gated channels, which mimicked simulation models suggesting MIL and DMN could bind to voltage gated sodium channels.
“MIL or DMN could form many non-covalent bonds with residues inside the ion channel (Nav 1.2), which affected the transport of sodium ions and the firing of the action potential,” the study states.
“Our docking results of DMN and MIL could also well support this principle and the distance from the DEE site and the strength of the interaction directly affect the inhibition of ion access.
“This might be the key mechanism for DMN and MIL to reduce VGSCs and the inhibition of action potential.
Certainly, the interaction between MIL, DMN and DEE site in Nav1.2 is just affecting the blocking of ion access slightly, which is hardly rank with the interaction between reported peptidic blocker or small-molecule blockers.”
Source: Mol. Nutr. Food Res
Published online: doi.org/10.1002/mnfr.202100210
“Flavonoid-Like Components of Peanut Stem and Leaf Extract Promote Sleep by Decreasing Neuronal Excitability”
Authors: Rui Guo et al.
