Download PDF
Planta Med 2015; 81(03): 185-192
DOI: 10.1055/s-0034-1396150
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Essential Oil of Syzygium aromaticum Reverses the Deficits of Stress-Induced Behaviors and Hippocampal p-ERK/p-CREB/Brain-Derived Neurotrophic Factor Expression

Bin-Bin Liu
1   Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, P. R. China
,
Liu Luo
1   Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, P. R. China
,
Xiao-Long Liu
1   Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, P. R. China
,
Di Geng
1   Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, P. R. China
,
Cheng-Fu Li
2   Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province, P. R. China
,
Shao-Mei Chen
2   Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province, P. R. China
,
Xue-Mei Chen
2   Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province, P. R. China
,
Li-Tao Yi
1   Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, P. R. China
,
Qing Liu
1   Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian Province, P. R. China
› Author Affiliations
Further Information

Publication History

received 01 February 2014
revised 23 November 2014

accepted 29 November 2014

Publication Date:
15 January 2015 (online)

Also available at
    Permissions and Reprints

Abstract

Syzygium aromaticum has been widely used in traditional medicine. Our study investigated the safety and antidepressant-like effects of the essential oil of S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight volatile constituents were identified in the essential oil of S. aromaticum. The single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity study. In a long-term repeated toxicity study of this essential oil (100, 200, and 400 mg/kg, p. o.), only 400 mg/kg induced a significant decrease in body weight. In addition, no significant changes in relative organ weights and histopathological analysis were observed in all doses of essential oil-treated mice compared with the control group. Furthermore, acute S. aromaticum essential oil administration by gavage exerted antidepressant-like effects in the forced swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg, p < 0.05). Long-term S. aromaticum essential oil treatment via gavage significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200 mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p-CREB, and brain-derived neurotrophic factor in mice exposed to chronic unpredictable mild stress. These results confirmed the safety of the essential oil of S. aromaticum and suggested that its potent antidepressant-like property might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF pathway in rats exposed to chronic unpredictable mild stress.

Key words

Syzygium aromaticum - Myrtaceae - essential oil - antidepressant - brain-derived neurotrophic factor - toxicity

Supporting Information

 

  • References

  • 1 Pilkington K, Kirkwood G, Rampes H, Fisher P, Richardson J. Homeopathy for depression: a systematic review of the research evidence. Homeopathy 2005; 94: 153-163
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS. National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289: 3095-3105
    CrossrefPubMedGoogle Scholar
  • 3 Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011; 21: 655-679
    Google Scholar
  • 4 Frey BN, Lord C, Soares CN. Depression during menopausal transition: a review of treatment strategies and pathophysiological correlates. Menopause Int 2008; 14: 123-128
    PubMedGoogle Scholar
  • 5 Lopez AD, Murray CC. The global burden of disease, 1990–2020. Nat Med 1998; 4: 1241-1243
    CrossrefPubMedGoogle Scholar
  • 6 Kalemba D, Kunicka A. Antibacterial and antifungal properties of essential oils. Curr Med Chem 2003; 10: 813-829
    CrossrefPubMedGoogle Scholar
  • 7 Chami F, Chami N, Bennis S, Bouchikhi T, Remmal A. Oregano and clove essential oils induce surface alteration of Saccharomyces cerevisiae . Phytother Res 2005; 19: 405-408
    CrossrefPubMedGoogle Scholar
  • 8 Mari M, Bertolini P, Pratella GC. Non-conventional methods for the control of post-harvest pear diseases. J Appl Microbiol 2003; 94: 761-766
    CrossrefPubMedGoogle Scholar
  • 9 Zheng GQ, Kenney PM, Lam LK. Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic agents. J Nat Prod 1992; 55: 999-1003
    CrossrefPubMedGoogle Scholar
  • 10 Lionnet L, Beaudry F, Vachon P. Intrathecal eugenol administration alleviates neuropathic pain in male Sprague-Dawley rats. Phytother Res 2010; 24: 1645-1653
    CrossrefPubMedGoogle Scholar
  • 11 Halder S, Mehta AK, Kar R, Mustafa M, Mediratta PK, Sharma KK. Clove oil reverses learning and memory deficits in scopolamine-treated mice. Planta Med 2011; 77: 830-834
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Son H, Banasr M, Choi M, Chae SY, Licznerski P, Lee B, Voleti B, Li N, Lepack A, Fournier NM, Lee KR, Lee IY, Kim J, Kim JH, Kim YH, Jung SJ, Duman RS. Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress. Proc Natl Acad Sci U S A 2012; 109: 11378-11383
    CrossrefPubMedGoogle Scholar
  • 13 Islamuddin M, Sahal D, Afrin F. Apoptosis-like death in Leishmania donovani promastigotes induced by eugenol-rich oil of Syzygium aromaticum . J Med Microbiol 2014; 63: 74-85
    CrossrefPubMedGoogle Scholar
  • 14 China Pharmacopoeia Committee. Pharmacopoeia of P. R. China. Part 1. Beijing: Peopleʼs Health Publishing House; 2010: 4
    Google Scholar
  • 15 Li J, Yu Y, Yang Y, Liu X, Zhang J, Li B, Zhou X, Niu J, Wei X, Liu Z. A 15-day oral dose toxicity study of aspirin eugenol ester in Wistar rats. Food Chem Toxicol 2012; 50: 1980-1985
    CrossrefPubMedGoogle Scholar
  • 16 Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985; 85: 367-370
    CrossrefPubMedGoogle Scholar
  • 17 Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977; 229: 327-336
    PubMedGoogle Scholar
  • 18 Willner P. Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 1997; 134: 319-329
    CrossrefPubMedGoogle Scholar
  • 19 Zhu WL, Wang SJ, Liu MM, Shi HS, Zhang RX, Liu JF, Ding ZB, Lu L. Glycine site N-methyl-D-aspartate receptor antagonist 7-CTKA produces rapid antidepressant-like effects in male rats. J Psychiatry Neurosci 2013; 38: 306-316
    CrossrefPubMedGoogle Scholar
  • 20 Iijima M, Fukumoto K, Chaki S. Acute and sustained effects of a metabotropic glutamate 5 receptor antagonist in the novelty-suppressed feeding test. Behav Brain Res 2012; 235: 287-292
    CrossrefPubMedGoogle Scholar
  • 21 Prasad SN. Muralidhara. Neuroprotective efficacy of eugenol and isoeugenol in acrylamide-induced neuropathy in rats: behavioral and biochemical evidence. Neurochem Res 2013; 38: 330-345
    CrossrefPubMedGoogle Scholar
  • 22 Garabadu D, Shah A, Ahmad A, Joshi VB, Saxena B, Palit G, Krishnamurthy S. Eugenol as an anti-stress agent: modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress. Stress 2011; 14: 145-155
    PubMedGoogle Scholar
  • 23 Seol GH, Shim HS, Kim PJ, Moon HK, Lee KH, Shim I, Suh SH, Min SS. Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats. J Ethnopharmacol 2010; 130: 187-190
    CrossrefPubMedGoogle Scholar
  • 24 Sah SP, Mathela CS, Chopra K. Involvement of nitric oxide (NO) signalling pathway in the antidepressant activity of essential oil of Valeriana wallichii Patchouli alcohol chemotype. Phytomedicine 2011; 18: 1269-1275
    CrossrefPubMedGoogle Scholar
  • 25 Hayley S, Anisman H. Neurotrophic paths in the treatment of depression. J Psychiatry Neurosci 2013; 38: 291-293
    CrossrefPubMedGoogle Scholar
  • 26 Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001; 24: 677-736
    CrossrefPubMedGoogle Scholar
  • 27 Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 2003; 60: 804-815
    CrossrefPubMedGoogle Scholar
  • 28 Karege F, Vaudan G, Schwald M, Perroud N, La Harpe R. Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res 2005; 136: 29-37
    CrossrefPubMedGoogle Scholar
  • 29 Zhang Y, Gu F, Chen J, Dong W. Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat. Brain Res 2010; 1366: 141-148
    CrossrefPubMedGoogle Scholar
  • 30 Lu B. BDNF and activity-dependent synaptic modulation. Learn Mem 2003; 10: 86-98
    CrossrefPubMedGoogle Scholar
  • 31 Duric V, Banasr M, Licznerski P, Schmidt HD, Stockmeier CA, Simen AA, Newton SS, Duman RS. A negative regulator of MAP kinase causes depressive behavior. Nat Med 2010; 16: 1328-1332
    CrossrefPubMedGoogle Scholar
  • 32 Feng SF, Shi TY, Fan Y, Wang WN, Chen YC, Tan QR. Long-lasting effects of chronic rTMS to treat chronic rodent model of depression. Behav Brain Res 2012; 232: 245-251
    CrossrefPubMedGoogle Scholar
  • 33 Qi X, Lin W, Li J, Li H, Wang W, Wang D, Sun M. Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress. Neurobiol Dis 2008; 31: 278-285
    CrossrefPubMedGoogle Scholar
  • 34 Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN. Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 2001; 77: 916-928
    CrossrefPubMedGoogle Scholar
  • 35 Yamada S, Yamamoto M, Ozawa H, Riederer P, Saito T. Reduced phosphorylation of cyclic AMP-responsive element binding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder. J Neural Transm 2003; 110: 671-680
    CrossrefPubMedGoogle Scholar
  • 36 Riccio A, Ahn S, Davenport CM, Blendy JA, Ginty DD. Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science 1999; 286: 2358-2361
    CrossrefPubMedGoogle Scholar
  • 37 Litchfield jr. JT, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 1949; 96: 99-113
    PubMedGoogle Scholar
  • 38 Yi LT, Li J, Liu Q, Geng D, Zhou YF, Ke XQ, Chen H, Weng LJ. Antidepressant-like effect of oleanolic acid in mice exposed to the repeated forced swimming test. J Psychopharmacol 2013; 27: 459-468
    CrossrefPubMedGoogle Scholar
  • 39 Yi LT, Li J, Liu BB, Luo L, Liu Q, Geng D. BDNF-ERK-CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice. J Psychiatry Neurosci 2014; 39: 348-359
    CrossrefPubMedGoogle Scholar
  • 40 Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 2011; 69: 754-761
    CrossrefPubMedGoogle Scholar