Effectiveness of the Sleep Enhancement by Green Romaine Lettuce (Lactuca sativa) in a Rodent Model

Biol Pharm Bull. 2019;42(10):1726-1732. doi: 10.1248/bpb.b19-00454.

Abstract

This study was conducted to investigate the effects of the extracts of green romaine lettuce (GRE) on sleep enhancement. GRE contains 1071.7 and 199.2 µg/g of extracts of lactucin and lactucopicrin, respectively, known as sleep enhancement substances. When 100 mg/kg of GRE was administered orally, sleep latency and duration time were significantly increased compared to controls (p < 0.05). Rapid eye movement (REM) sleep decreased with 100 mg/kg of GRE administration and non-REM (NREM) sleep also increased. There was no significant difference between REM and NREM among the oral GRE administration groups receiving 100, 120, and 160 mg/kg GRE. In the caffeine-induced insomnia model, total sleep time was significantly increased by 100 mg/kg GRE administration compared to the caffeine-treated group (p < 0.05). In addition, GRE inhibited the binding of [3H]-flumazenil in a concentration-dependent manner, and affinity of both lactucin and lactucopicrin to gamma-aminobutyric acid (GABA)A-benzodiazepine (BDZ) receptor was 80.7% and 55.9%, respectively. Finally, in the pentobarbital-induced sleep mouse model, the sleep enhancement effect of GRE was inhibited by flumazenil, an antagonist of BDZ. Thus, these results demonstrate that GRE acts via a GABAergic mechanism to promote sleep in a rodent model.

Keywords: Lactuca sativa; electroencephalogram; lactone; pentobarbital; rodent model; sleep.

MeSH terms

  • Animals
  • Lactones / analysis
  • Lactones / pharmacology*
  • Lactuca*
  • Male
  • Mice, Inbred ICR
  • Phorbols / analysis
  • Phorbols / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism
  • Sesquiterpenes / analysis
  • Sesquiterpenes / pharmacology*
  • Sleep / drug effects*

Substances

  • Lactones
  • Phorbols
  • Plant Extracts
  • Receptors, GABA-A
  • Sesquiterpenes
  • intybin
  • lactucin