Abstract

Ganoderma resinaceum is a valuable Chinese medicine. This study aimed to investigate whether a G. resinaceum alcohol extract (GRAE) improves sleep, and analyze the potential mechanism. After 30 days of continuous administration of GRAE at various doses, GRAE (1,000 mg/kg.bw) prolonged pentobarbital sodium-induced sleep, increased the rate of sleeping in mice treated with a subthreshold dose of pentobarbital sodium, and shortened sleep latency. The mice brain was analyzed using UPLC-MS/MS and RNA-sequencing. Metabolomics analysis revealed that 73 metabolites in the high-dose (HD) group had changed significantly, mainly in amino acids and their derivatives, especially the accumulation of L-glutamine and PGJ2 (11-oxo-15S-hydroxy-prosta-5Z, 9, 13E-trien-1-oic acid). Transcriptome analysis revealed 500 differential genes between HD and control groups, mainly enriched in neuroactive ligand-receptor interaction, amphetamine addiction, and cocaine addiction pathways. The conjoint analysis of the transcriptome and metabolome showed that the biosynthesis of L-glutamine might be regulated by Homer1, Homer3, and Grin3b. This suggests that GRAE may affect L-glutamine accumulation by regulating the expression of these genes. This study showed that GRAE may prolong the sleep time of mice by reducing the accumulation of L-glutamine and deepens our understanding of the regulatory network between certain genes and L-glutamine.

Highlights

  • Sleep is an important process in the maintenance of health [1]

  • This study showed that 30 days of G. resinaceum alcohol extract (GRAE) (1,000 mg/kg.bw) administration can prolong pentobarbital sodium-induced sleep in mice, increase the sleeping rate in mice treated with a subthreshold pentobarbital sodium dose, and shorten the sleep latency

  • This study investigated the effects of different concentrations of GRAE on the sleep time of mice

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Summary

Introduction

Sleep is an important process in the maintenance of health [1]. Chronic insomnia may cause regulatory imbalances, leading to various complications [2, 3]. It is estimated that over one-third of people suffer from insomnia, and the frequency is increasing [4]. Most sleep-inducing medicines are synthetic and cause major side effects, such as muscle relaxation, memory loss, and drug dependence [5]. Benzodiazepines, the primary drugs used to treat sleep disorders, mainly act on the central nervous system, and long-term use has side effects such as tolerance and dependency [6]. A safe and efficient alternative is needed to improve sleep quality

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