Sedative-hypnotic and anxiolytic effects and the mechanism of action of aqueous extracts of peanut stems and leaves in mice

J Sci Food Agric. 2018 Oct;98(13):4885-4894. doi: 10.1002/jsfa.9020. Epub 2018 May 17.

Abstract

Introduction: Peanut stems and leaves (PSL) have traditionally been used as both a special food and a herbal medicine in Asia. The sedative-hypnotic and anxiolytic effects of PSL have been recorded in classical traditional Chinese literature, and more recently by many other researchers. In a previous study, four sleep-related ingredients (linalool, 5-hydroxy-4',7-dimethoxyflavanone, 2'-O-methylisoliquiritigenin and ferulic acid), among which 5-hydroxy-4',7-dimethoxyflavanone and 2'-O-methylisoliquiritigenin were newly found in Arachis species, were screened by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS). In the current study, quantitative examination of the above four ingredients was conducted. Serious fundamental functional studies were done in mice, including locomotor activity, direct sleep tests, pentobarbital-induced sleeping time tests, subthreshold dose of pentobarbital tests and barbital sodium sleep incubation period tests, to determine the material base for the sedative-hypnotic and anxiolytic effects of aqueous extracts of PSL. Furthermore, neurotransmitter levels in three brain regions (cerebrum, cerebellum and brain stem) were determined using UHPLC coupled with triple-quadrupole mass spectrometry (UHPLC/QQQ-MS) in order to elucidate the exact mechanism of action.

Results: Aqueous extract of PSL at a dose of 500 mg kg-1 (based on previous experience), along with different concentrations of the above four functional ingredients (189.86 µg kg-1 linalool, 114.75 mg kg-1 5-hydroxy-4',7-dimethoxyflavanone, 32.4mg kg-1 2'-O-methylisoliquiritigenin and 44.44 mg kg-1 ferulic acid), had a sedative-hypnotic effect by affecting neurotransmitter levels in mice.

Conclusion: The data demonstrate that these four ingredients are the key functional factors for the sedative-hypnotic and anxiolytic effects of PSL aqueous extracts and that these effects occur via changes in neurotransmitter levels and pathways. © 2018 Society of Chemical Industry.

Keywords: four key functional factors; mechanism of action; neurotransmitter level; peanut stems and leaves; sedative effect.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / administration & dosage*
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / isolation & purification
  • Anxiety / drug therapy*
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Arachis / chemistry*
  • Brain / metabolism
  • Chromatography, High Pressure Liquid
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Hypnotics and Sedatives / chemistry
  • Hypnotics and Sedatives / isolation & purification
  • Male
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Neurotransmitter Agents / metabolism
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Leaves / chemistry
  • Plant Stems / chemistry
  • Sleep / drug effects

Substances

  • Anti-Anxiety Agents
  • Hypnotics and Sedatives
  • Neurotransmitter Agents
  • Plant Extracts