Protective Effect of St. John’s Wort (Hypericum perforatum) Extract on 72-Hour Sleep Deprivation-Induced Anxiety-Like Behavior and Oxidative Damage in Mice

Abstract

Sleep disruption or poor quality of sleep is a common problem associated with depression. Antidepressant drugs have been reported to improve the quality of sleep and behavior. The present study was undertaken to explore the therapeutic potential of Hypericum perforatum (St. John’s wort) on behavioral alterations and oxidative damage induced by sleep deprivation in mice. Male laca mice (n = 6 - 10 in each group) were sleep deprived for 72 hours using the grid suspended over water method. Standardized Hypericum perforatum extract and imipramine were administered for five days, starting two days before sleep deprivation. Alterations in body weight, motor activity, anxiety like behavior (mirror chamber, plus maze, zero maze) and oxidative stress parameters (reduced glutathione, catalase, lipid peroxidation and nitrite levels) were observed after drug treatment in sleep-deprived animals. 72-hour sleep deprivation significantly altered body weight, locomotor activity and produced anxiety-like behavior and oxidative damage (depleted reduced glutathione, catalase activity and increased lipid peroxidation and nitrite activity) as compared to the naïve (placed on sawdust) animals (P < 0.05). Treatment with either St. John’s wort (200 and 400 mg/kg, p. o.) or with imipramine (10 mg/kg, i. p.) significantly improved body weight, locomotor activity, antianxiety and antioxidant effect as compared to the control group (sleep deprived) (P < 0.05). Co-administration of John’s wort (200 mg/kg, p. o.) with imipramine (10 mg/kg, i. p.) further improved body weight, locomotor activity, antianxiety effect as well as reduced oxidative damage in sleep-deprived animal as compared to their effect per se (P < 0.05). The present study suggests that there is therapeutic potential of St. John’s wort in the management of sleep deprivation-induced anxiety-like behavior and oxidative damage.

Key words

Sleep - sleep deprivation - antidepressants - St. John’s wort - Hypericum perforatum - Hypericaceae - imipramine - oxidative stress

References

• 1 Berger R J. Bioenergetic functions of sleep and activity rhythms and their possible relevance to aging.  FedProc. 1975;  34 7-102.
• 2 Bergmann B M, Everson C A, Kushida C A, Fang V S, Leitch C A, Schoeller D A. et al . Sleep deprivation in the rat. V. Energy use and mediation.  Sleep. 1989;  12 31-41.
• 3 Suchecki D, Tiba P A, Tufik S. Hormonal and behavioral responses of paradoxical sleep-deprived rats to the elevated plus maze.  J Neuroendocrinol. 2002;  14 549-54.
• 4 Rechtschaffen A, Bergmann B M, Everson C A, Gulliland M A. Sleep deprivation in the rat: X Integration and discussion of the findings.  Sleep. 2002;  25 68-87.
• 5 Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine fuction.  Lancet. 1999;  354 1435-9.
• 6 Ramananthan L, Gulayani S, Nienhuis R, Siegel J M. Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem.  Neuroreport. 2002;  11 1387-90.
• 7 Kupfer D J, Frank E. The relationship of EEG sleep to vital depression.  J Affect Disord. 1984;  7 249-63.
• 8 Kupfer D J, Foster F G, Coble P, McPartland R J, Ulrich R F. The application of EEG sleeps for the differential diagnosis of affective disorders.  Am J Psychiatry. 1978;  135 69-74.
• 9 Viot-Blanc V. Biological models of depression: effect of antidepressants on sleep.  Encephale. 1995;  7 35-40.
• 10 Singewald N, Sinner C, Hetzenauer A, Sartori S B, Murck H. Magnesium-deficient diet alters depression- and anxiety-related behavior in mice-influence of desipramine and Hypericum perforatum extract.  Neuropharmacology. 2004;  47 1189-97.
• 11 Genovesa T, Mazzon E, Menegazzi M, Di Paola R, Muia C, Crisafulli Bramanti P. et al . Neuroprotection and enhanced recovery with Hypericum perforatum extract after experimental spinal cord injury in mice.  Shock. 2006;  25 608-17.
• 12 Greeson J M, Sanford B, Monti D A. St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.  Psychopharmacology. 2001;  153 402-14.
• 13 Shinomiya K, Shigemoto Y, Okuma C, Mio M, Kamei C. Effects of short- acting hypnotics on sleep latency in rats placed on grid suspended over water.  Eur J Pharmacol. 2003;  460 139-44.
• 14 Reddy D S, Kulkarni S K. Possible role of nitric oxide in the nootropic and antiamnesic effects of neurosteroids on aging and dizocilpine- induced learning impairment.  Brain Res. 1998;  799 215-29.
• 15 Kulkarni S K, Reddy D S. Animal behavioral models for testing antianxiety agents.  Method Find Exp Clin Pharmacol. 1996;  18 219-30.
• 16 Shepherd J K, Grewal S S. Behavioral and pharmacological characterization of the elevated ”zero maze” as a model of anxiety.  J Psychopharmacol. 1994;  116 56-64.
• 17 Kulkarni S K. Hand book of experimental pharmacology, 3rd edition.  Delhi: Vallabh. Prakashan;  1999 117-8.
• 18 Wills E D. Mechanism of lipid peroxide formation in animal tissues.  Biochem J. 1966;  99 667-76.
• 19 Ellman G L. Tissue sulfhydryl groups.  Arch Biochem Biophys. 1959;  82 48 670-7.
• 20 Green L C, Wagner D A, Glagowski J. Analysis of nitrate, nitrite and [¹⁵N] nitrate in biological fluids.  Anal. Biochem1982;  126 131-8.
• 21 Luck H. Catalase In: Bergmeyer HU, editor. Methods of enzymatic analysis.  New York: Academic. Press;  1971 885-93.
• 22 Lowry O H, Rosenberg N J, Farr A L, Randall R J. Protein measurement with the Folin-phenol reagent.  J Biol Chem. 1951;  193 265-75.
• 23 Schulz H, Jobert M. Effects of Hypericum extract on the sleep EEG in older volunteers.  J Geriatr Psychiatry Neurol. 1994;  7 S39-43.
• 24 Bhattacharya S K, Chakrabarti A, Chatterjee S S. Activity profiles of two hyperforin-containing Hypericum extracts in behavioral models.  Pharmacopsychiatry. 1998;  31 22-9.
• 25 Chatterjee S, Filippov V, Lishko P, Maximyuk O, Nöldner M, Krishtal O. Hyperforin attenuates various ionic conductance mechanisms in the isolated hippocampal neurons of rat.  Life Sci. 1999;  65 2395-405.
• 26 Feuillade P, Pringuey D, Belugou J L, Robert P, Darcourt G. Trimipramine: acute and lasting effects on sleep in healthy and major depressive subjects.  J Affect Disord. 1992;  24 135-45.
• 27 Nicholson A N, Pascoe P A. 5-Hydroxytryptamine and noradrenaline uptake inhibition: studies on sleep in man.  Neuropharmacology. 1986;  25 1079-83.
• 28 Cheung Z H, So K F, Lu Q, Yip H K, Wu W, Shan J J. et al . Enhanced survival and regeneration of axotomized retinal ganglion cells by a mixture of herbal extracts.  J Neurotrauma. 2002;  19 369-78.
• 29 Muller W E, Singer A, Wonneman M, Hafner U, Rolli M, Schafer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of Hypericum extract.  Pharmacopsychiatry. 1998;  31 16-21.
• 30 Greeson J M, Sanford B, Monti D A. St. John’s Wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.  Psychopharmacology. 2001;  153 402-14.