Quercetin-3-<i>O</i>-glucuronide in the Ethanol Extract of Lotus Leaf (<i>Nelumbo nucifera</i>) Enhances Sleep Quantity and Quality in a Rodent Model via a GABAergic Mechanism

• Main Authors: Singeun Kim, Ki-Bae Hong, Kyungae Jo, Hyung Joo Suh
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Molecules
• Subjects: <i>Nelumbo nucifera</i>; sleep duration; non-rapid eye movement sleep; quercetin-3-<i>O</i>-glucuronide
• Online Access: https://www.mdpi.com/1420-3049/26/10/3023

Current pharmacological treatments for insomnia carry several and long-term side effects. Therefore, natural products without side effects are warranted. In this study, the sleep-promoting activity of the lotus leaf (<i>Nelumbo nucifera</i>) extract was assessed using ICR mice and Sprague Dawley rats. A pentobarbital-induced sleep test and electroencephalogram analysis were conducted to measure sleep latency time, duration, and sleep architecture. The action mechanism of the extract was evaluated through ligand binding experiments. A high dose (300 mg/kg) of the ethanolic lotus leaf extract significantly increased sleep duration compared to the normal group (<i>p</i> < 0.01). Administration of low (150 mg/kg) and high doses (300 mg/kg) of the extract significantly increased sleep quality, especially the relative power of theta waves (<i>p</i> < 0.05), compared to the normal group. Furthermore, caffeine and lotus leaf extract administration significantly recovered caffeine-induced sleep disruption (<i>p</i> < 0.001), and the sleep quality was similar to that of the normal group. Additionally, ligand binding assay using [³H]-flumazenil revealed that quercetin-3<i>-O-</i>glucuronide contained in the lotus leaf extract (77.27 μg/mg of extract) enhanced sleep by binding to GABA_A receptors. Collectively, these results indicated that the lotus leaf extract, particularly quercetin-3-<i>O</i>-glucuronide, exhibits sleep quantity- and quality-enhancing activity via the GABAergic pathway.