(–)-Epigallocatechin-3-O-Gallate Augments Pentobarbital-Induced Sleeping Behaviors Through Cl⁻ Channel Activation

Abstract

This experiment investigated whether (-)-epigallocatechin-3-O-gallate (EGCG) (5-20 mg/kg, p.o.) has hypnotic effects and/or enhances pentobarbital-induced sleeping behaviors and whether these effects are mediated by γ-aminobutyric acid (GABA) receptors. EGCG prolonged sleeping time induced by pentobarbital (42 mg/kg, i.p.) and reduced sleeping latency induced by pentobarbital similarly to muscimol (0.2 mg/kg, i.p.), a GABA(A) receptor agonist in mice. EGCG also increased sleeping rate and sleeping time when co-administered with pentobarbital (28 mg/kg, i.p.) at a subhypnotic dosage. In addition, EGCG and pentobarbital increased chloride (Cl(-)) influx in primary cultured cerebellar cells. EGCG and pentobarbital decreased GABA(A) receptors α-subunit expression and had no effect on the expression of β- and γ-subunits and of glutamic acid decarboxylase in the hippocampus of rats. In conclusion, the EGCG enhancement of Cl(-) influx may play an important role in pentobarbital-induced sleeping behaviors.

Sleep-Aids Derived from Natural Products

“…One is stimulant caffeine, and the other is EGCG which may be sedative. From our experiment, it was interesting that only EGCG from green tea augmented pentobarbital-induced sleeping time through Cl − channel activation ( Park et al ., 2011 ). This may suggest that EGCG counteracts caffeine-induced stimulant effects such as hyperactivity, arousal and anxiogenic effects ( Park et al ., 2010 ).…”

The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome

“…On the other hand, chronic treatment with polyphenolic green tea extracts enriched in EGCG decreased the expression of the GABAergic synaptic markers GAD67 and VGAT in the cortex of Ts65Dn mice (Souchet et al, 2015). Conversely, EGCG positively modulated GABA A -mediated transmission when administered acutely (Vignes et al, 2006; Park et al, 2011). Of note, a recently concluded clinical trial (TESDAD, NCT01699711) evaluating the efficacy of long-term green tea extract treatment on DS patients showed some behavioral improvements, although—as stated by the authors—below the threshold for clinical relevance in 2 out of 15 measured tests (de la Torre et al, 2016).…”

Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity

“…(−)-Epigallocatechin-3-gallate ( Figure 8 ) is the most active flavanol contained in green tea, the product of Camellia sinensis (Theaceae). Park et al, [ 117 ] suggested that its anxiolytic and sedative effects are mediated by GABA A receptors. In their in vitro and in vivo experiments, (−)-epigallocatechin-3-gallate (5–20 mg/kg, p.o.)…”