Nelumbo nucifera promotes non-rapid eye movement sleep by regulating GABAergic receptors in rat model

J Ethnopharmacol. 2021 Mar 1:267:113511. doi: 10.1016/j.jep.2020.113511. Epub 2020 Oct 23.

Abstract

Ethnopharmacological relevance: Nelumbo nucifera are used in folk medicine for anti-depressant, anti-convulsant, neuroprotective, and many other purposes.

Aim of the study: The present work evaluated the sleep potentiating effects of water extract from lotus seed in rat, and the neuropharmacological mechanisms underlying these effects.

Materials and methods: Pentobarbital-induced sleep test and electroencephalogram (EEG) analysis were applied to investigate sleep latency, duration, total sleeping time and sleep quality of Lotus extract. In addition, real-time PCR and HPLC analysis were applied to analyze the signaling pathway.

Results: We found that the amounts of the possible active compounds GABA (2.33 mg/g) and L-tryptophan (2.00 mg/g) were higher than quinidine (0.55 mg/g) and neferine (0.16 mg/g) in lotus seed extract. High dose (160 mg/kg) administration of lotus extract led to a tendency towards decreased sleep latency time and an increase in sleep duration time compared to the control group in a pentobarbital-induced sleep model (p < 0.05). After high dose administration, total sleep and NREM were significantly increased compared to control, while wake time and REM were significantly decreased. Lotus extract-treated rats showed significantly reduced wake time and increased sleep time in a caffeine-induced model of arousal. The transcription level of GABAA receptor, GABAB receptor, and serotonin receptor tended to increase with dose, and lotus extract showed a strong dose-dependent binding capacity to the GABAA receptor.

Conclusion: The above results strongly suggest that GABA contained in lotus seed extract acts as a sleep potentiating compound, and that sleep-potentiating activity involves GABAA receptor binding.

Keywords: GABA; GABA(A) receptor; Nelumbo nucifera; Sleep.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • GABA-A Receptor Agonists / isolation & purification
  • GABA-A Receptor Agonists / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nelumbo* / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Signal Transduction
  • Sleep / drug effects*
  • Sleep Aids, Pharmaceutical / isolation & purification
  • Sleep Aids, Pharmaceutical / pharmacology*
  • Sleep Latency / drug effects
  • Time Factors
  • gamma-Aminobutyric Acid / isolation & purification
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • GABA-A Receptor Agonists
  • Plant Extracts
  • Receptors, GABA-A
  • Sleep Aids, Pharmaceutical
  • gamma-Aminobutyric Acid