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

Singeun Kim,Hyung Joo Suh,Ki-Bae Hong,Kyungae Jo

doi:10.3390/molecules26103023

Singeun Kim, Hyung Joo Suh + Show 2 more

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https://doi.org/10.3390/molecules26103023

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Abstract

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 (Nelumbo nucifera) 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 (p < 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 (p < 0.05), compared to the normal group. Furthermore, caffeine and lotus leaf extract administration significantly recovered caffeine-induced sleep disruption (p < 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-O-glucuronide contained in the lotus leaf extract (77.27 μg/mg of extract) enhanced sleep by binding to GABAA receptors. Collectively, these results indicated that the lotus leaf extract, particularly quercetin-3-O-glucuronide, exhibits sleep quantity- and quality-enhancing activity via the GABAergic pathway.

Highlights

IntroductionInsomnia is caused by a wide variety of psychological factors, such as stress, depression, anxiety, and environmental factors, such as caffeine, alcohol, and cigarettes [1]
Insomnia is caused by a wide variety of psychological factors, such as stress, depression, anxiety, and environmental factors, such as caffeine, alcohol, and cigarettes [1].Pharmacological treatments, such as benzodiazepines, non-benzodiazepines, and antidepressants, are used to suppress disruption of biological rhythms and the onset of diseases due to insomnia; chronic use of these drugs show many side effects due to resistance and dependence [2,3]
It has been reported that gamma-aminobutyric acid (GABA) and alkaloids contained in lotus seeds and leaves exert sedative and sleep effects via GABAA receptor binding

Summary

Introduction

Insomnia is caused by a wide variety of psychological factors, such as stress, depression, anxiety, and environmental factors, such as caffeine, alcohol, and cigarettes [1]. Pharmacological treatments, such as benzodiazepines, non-benzodiazepines, and antidepressants, are used to suppress disruption of biological rhythms and the onset of diseases due to insomnia; chronic use of these drugs show many side effects due to resistance and dependence [2,3]. Jujube (Ziziphus jujube), Hope (Humulus lupulus), Valerian (Valeriana officinalis L.), and lotus (Nelumbo nucifera Gaertn) extracts are natural substances and are used worldwide owing to their relaxation and sleep-improving effects as well as safety [3,4,5,6].

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