DOI QR코드

DOI QR Code

Alpha-Asarone, a Major Component of Acorus gramineus, Attenuates Corticosterone-Induced Anxiety-Like Behaviours via Modulating TrkB Signaling Process

  • Lee, Bombi (Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University) ;
  • Sur, Bongjun (The Graduate School of Basic Science of Korean Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Yeom, Mijung (Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University) ;
  • Shim, Insop (Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University) ;
  • Lee, Hyejung (Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University) ;
  • Hahm, Dae-Hyun (Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University)
  • Received : 2013.12.27
  • Accepted : 2014.04.12
  • Published : 2014.06.30

Abstract

We investigated the anxiolytic-like activity of ${\alpha}$-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

Keywords

References

  1. Jindal A, Mahesh R, Kumar B. Anxiolytic-like effect of linezolid in experimental mouse models of anxiety. Prog Neuropsychopharmacol Biol Psychiatry. 2013;40:47-53. https://doi.org/10.1016/j.pnpbp.2012.09.006
  2. Marquez C, Nadal R, Armario A. Influence of reactivity to novelty and anxiety on hypothalamic-pituitary-adrenal and prolactin responses to two different novel environments in adult male rats. Behav Brain Res. 2006;168:13-22. https://doi.org/10.1016/j.bbr.2005.10.004
  3. Saiyudthong S, Marsden CA. Acute effects of bergamot oil on anxiety-related behaviour and corticosterone level in rats. Phytother Res. 2011;25:858-862. https://doi.org/10.1002/ptr.3325
  4. de Andrade JS, Céspedes IC, Abrao RO, Dos Santos TB, Diniz L, Britto LR, Spadari-Bratfisch RC, Ortolani D, Melo-Thomas L, da Silva RC, Viana MB. Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis. Behav Brain Res. 2013;250:81-90. https://doi.org/10.1016/j.bbr.2013.04.031
  5. Krishnamurthy S, Garabadu D, Joy KP. Risperidone ameliorates post-traumatic stress disorder-like symptoms in modified stress re-stress model. Neuropharmacology. 2013;75:62-77. https://doi.org/10.1016/j.neuropharm.2013.07.005
  6. Huang Z, Zhong XM, Li ZY, Feng CR, Pan AJ, Mao QQ. Curcumin reverses corticosterone-induced depressive-like behavior and decrease in brain BDNF levels in rats. Neurosci Lett. 2011;493:145-148. https://doi.org/10.1016/j.neulet.2011.02.030
  7. Lee B, Shim I, Lee HJ, Yang Y, Hahm DH. Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats. Neurosci Lett. 2009;453:151-156. https://doi.org/10.1016/j.neulet.2009.01.076
  8. Skorzewska A, Lehner M, Wislowska-Stanek A, Krzascik P, Ziemba A, Plaznik A. The effect of chronic administration of corticosterone on anxiety- and depression-like behavior and the expression of GABA-A receptor alpha-2 subunits in brain structures of low- and high-anxiety rats. Horm Behav. 2014; 65:6-13. https://doi.org/10.1016/j.yhbeh.2013.10.011
  9. Lim H, Jang S, Lee Y, Moon S, Kim J, Oh S. Enhancement of anxiety and modulation of TH and pERK expressions in amygdala by repeated injections of corticosterone. Biomol Ther (Seoul). 2012;20:418-424. https://doi.org/10.4062/biomolther.2012.20.4.418
  10. Gregus A, Wintink AJ, Davis AC, Kalynchuk LE. Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats. Behav Brain Res. 2005;156:105-114. https://doi.org/10.1016/j.bbr.2004.05.013
  11. Taiwo AE, Leite FB, Lucena GM, Barros M, Silveira D, Silva MV, Ferreira VM. Anxiolytic and antidepressant-like effects of Melissa officinalis (lemon balm) extract in rats: Influence of administration and gender. Indian J Pharmacol. 2012;44:189-192. https://doi.org/10.4103/0253-7613.93846
  12. Husain GM, Chatterjee SS, Singh PN, Kumar V. Beneficial effect of Hypericum perforatum on depression and anxiety in a type 2 diabetic rat model. Acta Pol Pharm. 2011;68:913-918.
  13. Chen QX, Miao JK, Li C, Li XW, Wu XM, Zhang XP. Anticonvulsant activity of acute and chronic treatment with a-asarone from Acorus gramineus in seizure models. Biol Pharm Bull. 2013;36:23-30.
  14. Liang J, Huang B, Wang G. Chemical composition, antinociceptive and anti-inflammatory properties of essential oil from the roots of Illicium lanceolatum. Nat Prod Res. 2012;26:1712-1714. https://doi.org/10.1080/14786419.2011.603318
  15. Vohora SB, Shah SA, Dandiya PC. Central nervous system studies on an ethanol extract of Acorus calamus rhizomes. J Ethnopharmacol. 1990;28:53-62. https://doi.org/10.1016/0378-8741(90)90065-2
  16. Pages N, Maurois P, Delplanque B, Bac P, Stables JP, Tamariz J, Chamorro G, Vamecq J. Activities of ${\alpha}$-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties. Neurosci Res. 2010;68:337-344. https://doi.org/10.1016/j.neures.2010.08.011
  17. Manikandan S, Devi RS. Antioxidant property of alpha-asarone against noise-stress-induced changes in different regions of rat brain. Pharmacol Res. 2005;52:467-474. https://doi.org/10.1016/j.phrs.2005.07.007
  18. Limon ID, Mendieta L, Diaz A, Chamorro G, Espinosa B, Zenteno E, Guevara J. Neuroprotective effect of alpha-asarone on spatial memory and nitric oxide levels in rats injected with amyloid-beta((25-35)). Neurosci Lett. 2009;453:98-103. https://doi.org/10.1016/j.neulet.2009.02.011
  19. Mao QQ, Huang Z, Ip SP, Xian YF, Che CT. Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats. Behav Brain Res. 2012;227:305-309. https://doi.org/10.1016/j.bbr.2011.11.016
  20. Yi LT, Li J, Li HC, Zhou Y, Su BF, Yang KF, Jiang M, Zhang YT. Ethanol extracts from Hemerocallis citrina attenuate the decreases of brain-derived neurotrophic factor, TrkB levels in rat induced by corticosterone administration. J Ethnopharmacol. 2012;144:328-334. https://doi.org/10.1016/j.jep.2012.09.016
  21. Lee B, Sur BJ, Kwon S, Jung E, Shim I, Lee H, Hahm DH. Acupuncture stimulation alleviates corticosterone-induced impairments of spatial memory and cholinergic neurons in rats. Evid Based Complement Alternat Med. 2012;2012:670536.
  22. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York, USA: Academic Press; 1986. 54-85 p.
  23. Lee B, Sur B, Kwon S, Yeom M, Shim I, Lee H, Hahm DH. Chronic administration of catechin decreases depression and anxiety-like behaviors in a rat model using chronic corticosterone injections. Biomol Ther (Seoul) 2013;21:313-322. https://doi.org/10.4062/biomolther.2013.004
  24. Huang C, Li WG, Zhang XB, Wang L, Xu TL, Wu D, Li Y. ${\alpha}$-asarone from Acorus gramineus alleviates epilepsy by modulating A-type GABA receptors. Neuropharmacology. 2013;65: 1-11. https://doi.org/10.1016/j.neuropharm.2012.09.001
  25. Geng Y, Li C, Liu J, Xing G, Zhou L, Dong M, Li X, Niu Y. Beta-asarone improves cognitive function by suppressing neuronal apoptosis in the beta-amyloid hippocampus injection rats. Biol Pharm Bull. 2010;33:836-843. https://doi.org/10.1248/bpb.33.836
  26. Gilani AU, Shah AJ, Ahmad M, Shaheen F. Antispasmodic effect of Acorus calamus Linn. is mediated through calcium channel blockade. Phytother Res. 2006;20:1080-1084. https://doi.org/10.1002/ptr.2000
  27. Liu L, Fang YQ. Analysis of the distribution of ${\beta}$-asarone in rat hippocampus, brainstem, cortex and cerebellum with gas chromatography-mass spectrometry (GC-MS). J Med Plants Res. 2011;5:1728-1734.
  28. Wang D, Wang X, Li X, Ye L. Preparation and characterization of solid lipid nanoparticles loaded with alpha-Asarone. PDA J Pharm Sci Technol. 2008;62:56-65.
  29. Nacher J, Pham K, Gil-Fernandez V, McEwen BS. Chronic restraint stress and chronic corticosterone treatment modulate differentially the expression of molecules related to structural plasticity in the adult rat piriform cortex. Neuroscience. 2004; 126:503-509. https://doi.org/10.1016/j.neuroscience.2004.03.038
  30. Wuppen K, Oesterle D, Lewicka S, Kopitz J, Plaschke K. A subchronic application period of glucocorticoids leads to rat cognitive dysfunction whereas physostigmine induces a mild neuroprotection. J Neural Transm. 2010;117:1055-1065. https://doi.org/10.1007/s00702-010-0441-4
  31. Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, Kunugi H. Chronic restraint stress causes anxietyand depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39:112-119. https://doi.org/10.1016/j.pnpbp.2012.05.018
  32. Waters P, McCormick CM. Caveats of chronic exogenous corticosterone treatments in adolescent rats and effects on anxiety-like and depressive behavior and hypothalamic-pituitary-adrenal (HPA) axis function. Biol Mood Anxiety Disord. 2011;1:4. https://doi.org/10.1186/2045-5380-1-4
  33. Fan JM, Chen XQ, Jin H, Du JZ. Gestational hypoxia alone or combined with restraint sensitizes the hypothalamic-pituitary-adrenal axis and induces anxiety-like behavior in adult male rat offspring. Neuroscience. 2009;159:1363-1373. https://doi.org/10.1016/j.neuroscience.2009.02.009
  34. Min L, Chen SW, Li WJ, Wang R, Li YL, Wang WJ, Mi XJ. The effects of angelica essential oil in social interaction and hole-board tests. Pharmacol Biochem Behav. 2005;81:838-842. https://doi.org/10.1016/j.pbb.2005.05.015
  35. Han H, Jung JK, Han SB, Nam SY, Oh KW, Hong JT. Anxiolytic-like effects of 4-O-methylhonokiol isolated from Magnolia officinalis through enhancement of GABAergic transmission and chloride influx. J Med Food. 2011;14:724-731. https://doi.org/10.1089/jmf.2010.1111
  36. Kokras N, Dalla C, Sideris AC, Dendi A, Mikail HG, Antoniou K, Papadopoulou-Daifoti Z. Behavioral sexual dimorphism in models of anxiety and depression due to changes in HPA axis activity. Neuropharmacology. 2012;62:436-445. https://doi.org/10.1016/j.neuropharm.2011.08.025
  37. Fox JH, Lowry CA. Corticotropin-releasing factor-related peptides, serotonergic systems, and emotional behavior. Front Neurosci. 2013;7:169.
  38. Kupferschmidt DA, Newman AE, Boonstra R, Erb S. Antagonism of cannabinoid 1 receptors reverses the anxiety-like behavior induced by central injections of corticotropin-releasing factor and cocaine withdrawal. Neuroscience. 2012;204:125-133. https://doi.org/10.1016/j.neuroscience.2011.07.022
  39. Park HJ, Shim HS, Kim H, Kim KS, Lee H, Hahm DH, Shim I. Effects of Glycyrrhizae Radix on repeated restraint stressinduced neurochemical and behavioral responses. Korean J Physiol Pharmacol. 2010;14:371-376. https://doi.org/10.4196/kjpp.2010.14.6.371
  40. Wang YC, Ho UC, Ko MC, Liao CC, Lee LJ. Differential neuronal changes in medial prefrontal cortex, basolateral amygdala and nucleus accumbens after postweaning social isolation. Brain Struct Funct. 2012;217:337-351. https://doi.org/10.1007/s00429-011-0355-4
  41. Sevgi S, Ozek M, Eroglu L. L-NAME prevents anxiety-like and depression-like behavior in rats exposed to restraint stress. Methods Find Exp Clin Pharmacol. 2006;28:95-99. https://doi.org/10.1358/mf.2006.28.2.977840
  42. Spasojevic N, Gavrilovic L, Dronjak S. Effects of repeated maprotiline and fluoxetine treatment on gene expression of catecholamine synthesizing enzymes in adrenal medulla of unstressed and stressed rats. Auton Autacoid Pharmacol. 2010;30:213-217. https://doi.org/10.1111/j.1474-8673.2010.00458.x
  43. Dalle Molle R, Portella AK, Goldani MZ, Kapczinski FP, Leistner-Segal S, Salum GA, Manfro GG, Silveira PP. Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels. Transl Psychiatry. 2012;2:e195. https://doi.org/10.1038/tp.2012.126
  44. Thompson Ray M, Weickert CS, Wyatt E, Webster MJ. Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci. 2011;36:195-203. https://doi.org/10.1503/jpn.100048
  45. Yang CH, Huang CC, Hsu KS. Behavioral stress modifies hippocampal synaptic plasticity through corticosterone-induced sustained extracellular signal-regulated kinase/mitogen-activated protein kinase activation. J Neurosci. 2004;24:11029-11034. https://doi.org/10.1523/JNEUROSCI.3968-04.2004
  46. Fahnestock M, Marchese M, Head E, Pop V, Michalski B, Milgram WN, Cotman CW. BDNF increases with behavioral enrichment and an antioxidant diet in the aged dog. Neurobiol Aging. 2012;33:546-554. https://doi.org/10.1016/j.neurobiolaging.2010.03.019

Cited by

  1. A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models vol.20, pp.10, 2014, https://doi.org/10.3390/molecules201018620
  2. Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats vol.10, pp.11, 2014, https://doi.org/10.1371/journal.pone.0142424
  3. β-Asarone Mitigates Amyloidosis and Downregulates RAGE in a Transgenic Mouse Model of Alzheimer’s Disease vol.36, pp.1, 2014, https://doi.org/10.1007/s10571-015-0226-2
  4. Decreased Interleukin-4 Release from the Neurons of the Locus Coeruleus in Response to Immobilization Stress vol.2016, pp.None, 2016, https://doi.org/10.1155/2016/3501905
  5. Biological Properties of Some Volatile Phenylpropanoids vol.11, pp.10, 2014, https://doi.org/10.1177/1934578x1601101041
  6. Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration vol.43, pp.11, 2014, https://doi.org/10.1080/03639045.2017.1349783
  7. Pharmacology and toxicology of α- and β-Asarone: A review of preclinical evidence vol.32, pp.None, 2014, https://doi.org/10.1016/j.phymed.2017.04.003
  8. α-Asarone in management of sleep deprivation induced memory deficits and anxiety in rat model vol.17, pp.1, 2014, https://doi.org/10.1007/s41105-018-0181-7
  9. Anti-Amyloidogenic Effects of Asarone Derivatives From Perilla frutescens Leaves Against Beta-Amyloid Aggregation and Nitric Oxide Production vol.24, pp.23, 2019, https://doi.org/10.3390/molecules24234297
  10. Anxiolytic Effect of Essential Oils and Their Constituents: A Review vol.67, pp.50, 2014, https://doi.org/10.1021/acs.jafc.9b00433