Polygonatum sibiricum rhizome promotes sleep by regulating non-rapid eye movement and GABAergic/serotonergic receptors in rodent models

Abstract

The aim of this study is to investigate the sleep-promoting effect of a water extract of the Polygonatum sibiricum rhizome (PSE) in rodent models. PSE contained oleamide (0.10 mg/g extract) and glyceryl monolinoleate (0.17 mg/g extract), which are recognized as sleep-promoting substances. In pentobarbital-induced sleep model at hypnotic level, PSE (160 mg/kg) administration significantly decreased sleep latency time by 29% (2.7 min) and increased sleep duration time by 70% (68.4 min) compared with the normal control (3.8 min and 40.7 min, respectively). In the electroencephalography (EEG) analysis of rats, PSE-mediated sleep promotion accompanied the change of sleep architecture including increase of non-rapid eye movement (NREM) and decrease of REM. This sleep promoting effect was more obvious in caffeine-induced awakening model; total sleep time was increased by 40% along with increased NREM by PSE treatment M 160 mg/kg. In addition, PSE significantly increased the protein and mRNA levels of GABA(A)-R2 and 5-HT1A receptor, the major sleep-related neurotransmitter receptors. Furthermore, glyceryl monolinoleate and oleamide effectively bound to GABA(A) receptor in a competitive binding assay. These results indicate that PSE-mediated sleep-promoting effect is associated with the extension of NREM and upregulation of GABA(A)-R2 and 5-HT1A, and is mediated by binding to the GABA(A) receptor in vertebrate models.