Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep


The objective of this study was to investigate the sleep-inducing effect of lettuce varieties and the extracts derived from romaine lettuce on pentobarbital-induced sleep. Romaine lettuce had a higher lactucin content (red romaine: 361.50 µg/g of extract, green romaine: 1071.67 µg/g of extract) compared to the green and red lettuce varieties. The seed and leaf extracts derived from romaine lettuce induced an increase in the sleep duration at low and high doses respectively. The seed extract of romaine lettuce showed higher content of polyphenols, including caftaric acid, chlorogenic acid, and chicoric acid, compared to the leaf extract. The IC50 value of the leaf extract for its DPPH radical-scavenging was significantly less (0.11 mg/mL) than that of the seed extract (0.21 mg/mL) (p < 0.05). Romaine lettuce is an interesting and valuable source of sleep potentiating material and contains antioxidant phenolics that protect from the oxidant stress caused by sleep disturbance.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 22 Suppl 2: S347–353 (1999)

    Google Scholar 

  2. 2.

    Richardson CE, Gradisar M, Barbero SC. Are cognitive “insomnia” processes involved in the development and maintenance of delayed sleep wake phase disorder? Sleep Med. Rev. 26: 1–8 (2016)

    Article  Google Scholar 

  3. 3.

    Ramakrishnan K, Scheid DC. Treatment options for insomnia. Am. Fam. Physician. 76: 517–526 (2007)

    Google Scholar 

  4. 4.

    Ni H, Simile C, Hardy AM. Utilization of complementary and alternative medicine by United States adults: results from the 1999 national health interview survey. Med. Care. 40: 353–358 (2002)

    Article  Google Scholar 

  5. 5.

    Ernst E. When natural is not harmless. Int. J. Clin. Pract. 60: 380–380 (2006)

    CAS  Article  Google Scholar 

  6. 6.

    Pearson NJ, Johnson LL, Nahin RL. Insomnia, trouble sleeping, and complementary and alternative medicine - Analysis of the 2002 National Health Interview Survey data. Arch. Intern. Med. 166: 1775–1782 (2006)

    Article  Google Scholar 

  7. 7.

    Sayyah M, Hadidi N, Kamalinejad M. Analgesic and anti-inflammatory activity of Lactuca sativa seed extract in rats. J. Ethnopharmacol. 92: 325–329 (2004)

    Article  Google Scholar 

  8. 8.

    Said S, Kashef HE, Mazar ME, Salama O. Phytochemical and pharmacological studies on Lactuca sativa seed oil. Fitoterapia. 67: 215–219 (1996)

    CAS  Google Scholar 

  9. 9.

    Arnous A, Makris DP, Kefalas P. Anthocyanin composition and colour characteristics of selected aged wines produced in Greece. J. Wine Res. 13: 23–34 (2002)

    Article  Google Scholar 

  10. 10.

    Quang DN, Hashimoto T, Nukada M, Yamamoto I, Tanaka M, Asakawa Y. Antioxidant activity of curtisians I-L from the inedible mushroom Paxillus curtisii. Planta Med. 69: 1063–1066 (2003)

    CAS  Article  Google Scholar 

  11. 11.

    Wang HC, Chen CR, Chang CMJ. Carbon dioxide extraction of ginseng root hair oil and ginsenosides. Food Chem. 72: 505–509 (2001)

    CAS  Article  Google Scholar 

  12. 12.

    Almajano MP, Carbo R, Delgado ME, Gordon MH. Effect of pH on the antimicrobial activity and oxidative stability of oil-in-water emulsions containing caffeic acid. J. Food Sci. 72: C258-C263 (2007)

    CAS  Article  Google Scholar 

  13. 13.

    Yang H, Lee YC, Han KS, Singh H, Yoon M, Park JH, Cho CW, Cho S. Green and gold kiwifruit peel ethanol extracts potentiate pentobarbital-induced sleep in mice via a GABAergic mechanism. Food Chem. 136: 160–163 (2013)

    CAS  Article  Google Scholar 

  14. 14.

    Abu-Reidah IM, Arráez-Román D, Quirantes-Piné R, Fernández-Arroyo S, Segura-Carretero A, Fernández-Gutiérrez A. HPLC–ESI-Q-TOF-MS for a comprehensive characterization of bioactive phenolic compounds in cucumber whole fruit extract. Food Res. Int. 46: 108–117 (2012)

    CAS  Article  Google Scholar 

  15. 15.

    Ferreres F, Gil MI, Castaner M, TomasBarberan FA. Phenolic metabolites in red pigmented lettuce (Lactuca sativa). Changes with minimal processing and cold storage. J. Agric. Food Chem. 45: 4249–4254 (1997)

    Article  Google Scholar 

  16. 16.

    Ceolin T, Heck R, Barbieri R, de Souza A, Rodrigues W, Vanini M. Medicinal plants used as sedative by ecological farmers from Southern Rio Grande do Sul State, Brazil. Rev. Enferm. UFPE On line. 3: 253–260 (2009)

    Google Scholar 

  17. 17.

    Wesołowska A, Nikiforuk A, Michalska K, Kisiel W, Chojnacka-Wójcik E. Analgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice. J. Ethnopharmacol. 107: 254–258 (2006)

    Article  Google Scholar 

  18. 18.

    Gromek D, Kisiel W, Klodzinska A, Chojnackawojcik E. Biologically-Active Preparations from Lactuca-Virosa L. Phytother. Res. 6: 285–287 (1992)

    CAS  Article  Google Scholar 

  19. 19.

    Koch-Weser J, Greenblatt DJ. The archaic barbiturate hypnotics. N. Engl. J. Med. 291: 790–791 (1974)

    CAS  Article  Google Scholar 

  20. 20.

    Yakoot M, Helmy S, Fawal K. Pilot study of the efficacy and safety of lettuce seed oil in patients with sleep disorders. Int. J. Gen. Med. 4: 451–456 (2011)

    Article  Google Scholar 

  21. 21.

    Ghorbani A, Rakhshandeh H, Sadeghnia HR. Potentiating effects of Lactuca sativa on pentobarbital-induced sleep. Iran J Pharm Res. 12: 401–406 (2013)

    Google Scholar 

  22. 22.

    Nicolle C, Cardinault N, Gueux E, Jaffrelo L, Rock E, Mazur A, Amouroux P, Remesy C. Health effect of vegetable-based diet: lettuce consumption improves cholesterol metabolism and antioxidant status in the rat. Clin. Nutr. 23: 605–614 (2004)

    CAS  Article  Google Scholar 

  23. 23.

    Rice-Evans C, Miller NJ. Total antioxidant status in plasma and body fluids. Methods Enzymol. 234: 279–293 (1994)

    CAS  Article  Google Scholar 

  24. 24.

    Chun OK, Kim DO, Moon HY, Kang HG, Lee CY. Contribution of individual polyphenolics to total antioxidant capacity of plums. J. Agric. Food Chem. 51: 7240–7245 (2003)

    CAS  Article  Google Scholar 

  25. 25.

    Kim DO, Chun OK, Kim YJ, Moon HY, Lee CY. Quantification of polyphenolics and their antioxidant capacity in fresh plums. J. Agric. Food Chem. 51: 6509–6515 (2003)

    CAS  Article  Google Scholar 

  26. 26.

    Brandwilliams W, Cuvelier ME, Berset C. Use of a Free-Radical Method to Evaluate Antioxidant Activity. Food Sci Technol-Leb. 28: 25–30 (1995)

    CAS  Article  Google Scholar 

  27. 27.

    Okawa M, Kinjo J, Nohara T, Ono M. DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity of flavonoids obtained from some medicinal plants. Biol. Pharm. Bull. 24: 1202–1205 (2001)

    CAS  Article  Google Scholar 

  28. 28.

    Singh R, Kiloung J, Singh S, Sharma D. Effect of paradoxical sleep deprivation on oxidative stress parameters in brain regions of adult and old rats. Biogerontology. 9: 153–162 (2008)

    CAS  Article  Google Scholar 

  29. 29.

    Hipolide DC, D’almeida V, Raymond R, Tufik S, Noberga JN. Sleep deprivation does not affect indices of necrosis or apoptosis in rat brain. Int. J. Neurosci. 112: 155–166 (2002)

    Article  Google Scholar 

  30. 30.

    Andersen ML, Martins PJ, D’Almeida V, Santos RF, Bignotto M, Tufik S. Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats. Exp. Gerontol. 39: 817–824 (2004)

    CAS  Article  Google Scholar 

  31. 31.

    Graves LA, Heller EA, Pack AI, Abel T. Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning. Learn. Mem. 10: 168–176 (2003)

    Article  Google Scholar 

  32. 32.

    Zhang L, Zhang HQ, Liang XY, Zhang HF, Zhang T, Liu FE. Melatonin ameliorates cognitive impairment induced by sleep deprivation in rats: role of oxidative stress, BDNF and CaMKII. Behav. Brain Res. 256: 72–81 (2013)

    CAS  Article  Google Scholar 

  33. 33.

    Dringen R, Pawlowski PG, Hirrlinger J. Peroxide detoxification by brain cells. J. Neurosci. Res. 79: 157–165 (2005)

    CAS  Article  Google Scholar 

Download references


This research was supported by the Ministry of Trade, Industry and Energy (MOTIE) and the Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region.

Author information



Corresponding author

Correspondence to Hyung Joo Suh.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kim, H.D., Hong, KB., Noh, D.O. et al. Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep. Food Sci Biotechnol 26, 807–814 (2017).

Download citation


  • Lettuce
  • Lactuca sativa
  • Sleep
  • Anti-radical