Anti-Stress Effect of Punica granatum L. Extract against Sleep Deprivation-Induced Impairment

석류 열수 추출물의 수면박탈을 유도한 Rat 모델에서의 항스트레스 효과

  • Na, Ju-Ryun (Bioresources and Technology) ;
  • Kim, Sunoh (Bioresources and Technology) ;
  • Jo, Ara (Jeonnam Institute of Natural Resources Research) ;
  • Bae, Donghyuck (Jeonnam Institute of Natural Resources Research) ;
  • Oh, Kyo-Nyeo (Jeonnam Institute of Natural Resources Research) ;
  • Kim, Yong Jae (Division of Food and Nutrition, Chonnam National University) ;
  • Lee, Yoo-Hyun (Department of Food Science and Nutrition, The University of Suwon) ;
  • Jun, Woojin (Division of Food and Nutrition, Chonnam National University)
  • Received : 2016.01.29
  • Accepted : 2016.09.29
  • Published : 2016.11.30


The anti-stress effects of Punica granatum L. (family Lythraceae, PG) on $H_2O_2$/corticosterone (CORT)-induced stress in cells and sleep-deprived rats were investigated. The PG extract showed neuroprotective effects in SH-SY5Y cells against $H_2O_2$/CORT-induced stress. Sleep deprivation led to behavioral, hormonal, and biochemical alterations in the animal model. The effects of P. granatum on physiological, behavioral, and biochemical parameters aggravated by sleep deprivation were investigated. Sleep deprivation impaired physiological (survival, body weight, and drowsiness scores) and behavioral (rotarod, passive avoidance, hot hyperalgesia, and Y maze) parameters as well as biochemical factors (cortisol, serotonin, dopamine, testosterone, and growth factor I contents in serum). These parameters were significantly recovered by PG extract in a concentration-dependent manner. The PG extract also enhanced catalase, superoxide dismutase, and non-enzymatic antioxidative activities such as glutathione compared to sleep-deprived rats. On the basis of these results, our findings suggest that Punica granatum prevents impairment of body functions induced by sleep deprivation and related oxidative damage.


Supported by : 산업통상자원부


  1. Pace-Schott EF, Hobson JA 2002. The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 3: 591-605.
  2. Reimund E. 1994. The free radical flux theory of sleep. Med Hypotheses 43: 231-233.
  3. Vollert C, Zagaar M, Hovatta I, Taneja M, Vu A, Dao A, Levine A, Alkadhi K, Salim S. 2011. Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: potential role of oxidative stress mechanisms. Behav Brain Res 224: 233-240.
  4. D'Almeida V, Hipólide DC, Azzalis LA, Lobo LL, Junqueira VB, Tufik S. 1997. Absence of oxidative stress following paradoxical sleep deprivation in rats. Neurosci Lett 235: 25-28.
  5. Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J. 2008. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320: 661-664.
  6. Shaygannia E, Bahmani M, Zamanzad B, Rafieian-Kopaei M. 2015. A review study on Punica granatum L. J Evid Based Complementary Altern Med 21: 221-227.
  7. Satomi H, Umemura K, Ueno A, Hatano T, Okuda T, Noro T. 1993. Carbonic anhydrase inhibitors from the pericarps of Punica granatum L.. Biol Pharm Bull 16: 787-790.
  8. Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D. 2005. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 16: 360-367.
  9. Lansky EP, Newman RA. 2007. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 109: 177-206.
  10. Jafri MA, Aslam M, Javed K, Singh S. 2000. Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats. J Ethnopharmacol 70: 309-314.
  11. Ahmed S, Wang N, Hafeez BB, Cheruvu VK, Haqqi TM. 2005. Punica granatum L. extract inhibits IL-$1{\beta}$-induced expression of matrix metalloproteinases by inhibiting the activation of MAP kinases and NF-${\kappa}$B in human chondrocytes in vitro. J Nutr 135: 2096-2102.
  12. Kaur G, Jabbar Z, Athar M, Alam MS. 2006. Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food Chem Toxicol 44: 984-993.
  13. Goshtasebi A, Mazari Z, Behboudi Gandevani S, Naseri M. 2015. Anti-hemorrhagic activity of Punica granatum L. flower (Persian Golnar) against heavy menstrual bleeding of endometrial origin: a double-blind, randomized controlled trial. Med J Islam Repub Iran 29: 199.
  14. Mori-Okamoto J, Otawara-Hamamoto Y, Yamato H, Yoshimura H. 2004. Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice. J Ethnopharmacol 92: 93-101.
  15. Choi SJ, Lee JH, Heo HJ, Cho HY, Kim HK, Kim CJ, Kim MO, Suh SH, Shin DH. 2011. Punica granatum protects against oxidative stress in PC12 cells and oxidative stressinduced Alzheimer's symptoms in mice. J Med Food 14: 695-701.
  16. Cohen HB, Dement WC. 1965. Sleep: changes in threshold to electroconvulsive shock in rats after deprivation of "paradoxical" phase. Science 150: 1318-1319.
  17. Watzman N, Barry H 3rd, Kinnard WJ Jr, Buckley JP. 1967. Influence of certain parameters on the performance of mice on the rotarod. Arch Int Pharmacodyn Ther 169: 362-374.
  18. Bae D, Seol H, Yoon HG, Na JR, Oh K, Choi CY, Lee DW, Jun W, Youl Lee K, Lee J, Hwang K, Lee YH, Kim S. 2012. Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of cognitive function induced by injection of ${\beta}$-amyloid in rats. Pharm Biol 50: 900-910.
  19. Fanselow MS, Bolles RC. 1979. Naloxone and shock-elicited freezing in the rat. J Comp Physiol Psychol 93: 736-744.
  20. Sarter M, Bodewitz G, Stephens DN. 1988. Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist beta-carbolines. Psychopharmacology (Berl) 94: 491-495.
  21. Calegare BF, Fernandes L, Tufik S, D'Almeida V. 2010. Biochemical, biometrical and behavioral changes in male offspring of sleep-deprived mice. Psychoneuroendocrinology 35: 775-784.
  22. Kumar S, Maheshwari KK, Singh V. 2008. Central nervous system activity of acute administration of ethanol extract of Punica granatum L. seeds in mice. Indian J Exp Biol 46: 811-816.
  23. Silva RH, Abilio VC, Kameda SR, Takatsu-Coleman AL, Carvalho RC, Ribeiro Rde A, Tufik S, Frussa-Filho R. 2007. Effects of 3-nitropropionic acid administration on memory and hippocampal lipid peroxidation in sleep-deprived mice. Prog Neuropsychopharmacol Biol Psychiatry 31: 65-70.
  24. Vidal C, Jacob J. 1986. Hyperalgesia induced by emotional stress in the rat: an experimental animal model of human anxiogenic hyperalgesia. Ann N Y Acad Sci 467: 73-81.
  25. Gunn A, Bobeck EN, Weber C, Morgan MM. 2011. The influence of non-nociceptive factors on hot-plate latency in rats. J Pain 12: 222-227.
  26. Kim Y, Laposky AD, Bergmann BM, Turek FW. 2007. Repeated sleep restriction in rats leads to homeostatic and allostatic responses during recovery sleep. Proc Natl Acad Sci U S A 104: 10697-10702.
  27. Rajaratnam SM, Arendt J. 2001. Health in a 24-h society. Lancet 358: 999-1005.
  28. Wu JL, Wu RS, Yang JG, Huang CC, Chen KB, Fang KH, Tsai HD. 2011. Effects of sleep deprivation on serum testosterone concentrations in the rat. Neurosci Lett 494: 124-129.
  29. Everson CA, Crowley WR. 2004. Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats. Am J Physiol Endocrinol Metab 286: E1060-1070.
  30. Foley NC, Bhogal SK, Teasell RW, Bureau Y, Speechley MR. 2006. Estimates of quality and reliability with the physiotherapy evidence-based database scale to assess the methodology of randomized controlled trials of pharmacological and nonpharmacological interventions. Phys Ther 86: 817-824.
  31. Newsholme EA, Acworth IN, Blomstrand E. 1987. Amino acids, brain neurotransmitters and a functional link between muscle and brain that is important in sustained exercise. John Libbey Eurotext Ltd., London, UK. p 127-133.
  32. Silva RH, Abílio VC, Takatsu AL, Kameda SR, Grassl C, Chehin AB, Medrano WA, Calzavara MB, Registro S, Andersen ML, Machado RB, Carvalho RC, Ribeiro Rde A, Tufik S, Frussa-Filho R. 2004. Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacology 46: 895-903.
  33. del Rio LA, Sandalio LM, Palma JM, Bueno P, Corpas FJ. 1992. Metabolism of oxygen radicals in peroxisomes and cellular implications. Free Radic Biol Med 13: 557-580.
  34. Moneim AEA. 2012. Antioxidant activities of Punica granatum (pomegranate) peel extract on brain of rats. J Med Plants Res 6: 195-199.
  35. Yaidikar L, Byna B, Thakur SR. 2014. Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxidative brain injury in rats. J Stroke Cerebrovasc Dis 23: 2869-2878.
  36. Braidy N, Selvaraju S, Essa MM, Vaishnav R, Al-Adawi S, Al-Asmi A, Al-Senawi H, Abd Alrahman Alobaidy A, Lakhtakia R, Guillemin GJ. 2013. Neuroprotective effects of a variety of pomegranate juice extracts against MPTP-induced cytotoxicity and oxidative stress in human primary neurons. Oxid Med Cell Longev 2013: 685909.
  37. Mizrahi M, Friedman-Levi Y, Larush L, Frid K, Binyamin O, Dori D, Fainstein N, Ovadia H, Ben-Hur T, Magdassi S, Gabizon R. 2014. Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD. Nanomedicine 10: 1353-1363.