Sedative-Hypnotic Effects of Glycine max Merr. Extract and Its Active Ingredient Genistein on Electric-Shock-Induced Sleep Disturbances in Rats

Int J Mol Sci. 2023 Apr 11;24(8):7043. doi: 10.3390/ijms24087043.

Abstract

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders.

Keywords: Glycine max Merr.; electric foot shock stress-induced insomnia; electroencephalography (EEG); sedative-hypnotic activity; sleep.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Corticotropin-Releasing Hormone* / pharmacology
  • Electroencephalography
  • Genistein / pharmacology
  • Genistein / therapeutic use
  • Glycine max / metabolism
  • Hypnotics and Sedatives / pharmacology
  • Hypnotics and Sedatives / therapeutic use
  • Rats
  • Receptor, Serotonin, 5-HT2C
  • Serotonin / metabolism
  • Sleep
  • Sleep Wake Disorders* / drug therapy
  • Sleep Wake Disorders* / etiology

Substances

  • Corticotropin-Releasing Hormone
  • Genistein
  • Serotonin
  • Receptor, Serotonin, 5-HT2C
  • Hypnotics and Sedatives
  • Antidepressive Agents

Grants and funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1A6A3A01086224) and National Research Foundation of Korea (NRF-2021R1A2C1093825) and World-home doctor Co. (2022).