Romaine lettuce/skullcap mixture improves sleep behavior in vertebrate models

Ki Bae Hong, Sung Hee Han, Yooheon Park, Hyung Joo Suh, Hyeon Son Choi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


The aim of this study is to investigate the effects of romaine lettuce leaves extract (RE), skullcap root extract (SE) and their mixture on sleep behaviors in vertebrate models. HPLC analysis showed that RE contains lactucopicrin (0.02±0.01mg/g extract), chlorogenic acid (4.05±0.03mg/g extract), caffeic acid (2.38±0.03mg/g extract), and chicoric acid (7.02±0.32mg/g extract) as main phenolic compounds, while SE includes baicalin (99.4±0.5mg/g extract), baicalein (8.28±0.21mg/g extract), and wogonin (3.09±0.32mg/g extract). The mixture of RE (100mg/g extract) and SE (40mg/g extract) increased total sleep time by 50.9% compared with the control in pentobarbital-induced sleep model. In electroencephalography (EEG) analysis, RE/SE mixture significantly increased Non-Rapid Eye Movement (NREM), in which delta wave was enhanced by around 40% compared with normal control, leading to the increase of sleep time. In caffeine-induced wake model, RE/SE mixture greatly decreased (53%) caffeine-induced wake time, showing a similar level to normal control. In addition, caffeine-induced decreased of NREM and delta wave effectively increased with RE/SE mixture; NREM and delta wave increased by 85% and 108%, respectively. Furthermore, RE/SE mixture was shown to bind to a gamma-aminobutyric acid type A (GABAA)-benzodiazepine (BZD) receptor stronger than RE or SE single extract. Taken together, RE/SE mixture effectively improved sleep behavior with the increase of NREM via GABAA-BZD receptor binding. RE/SE mixture can be used as an herbal agent for sleep disorders.

Original languageEnglish
Pages (from-to)1269-1276
Number of pages8
JournalBiological and Pharmaceutical Bulletin
Issue number8
Publication statusPublished - 2018


  • Gamma-aminobutyric acid (GABA) receptor
  • Non-rapid eye movement
  • Rodent model
  • Romaine lettuce
  • Skullcap
  • Sleep behavior

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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