Advertisement

Neurochemical Research

, Volume 43, Issue 8, pp 1519–1528 | Cite as

Honokiol Exerts Antidepressant Effects in Rats Exposed to Chronic Unpredictable Mild Stress by Regulating Brain Derived Neurotrophic Factor Level and Hypothalamus–Pituitary–Adrenal Axis Activity

  • Canmao Wang
  • Danna Gan
  • Jingang Wu
  • Minhui Liao
  • Xinghuan Liao
  • Weipeng Ai
Original Paper

Abstract

Honokiol (HNK), the main active component of Magnolia officinalis, has shown a variety of pharmacological activities. In the present study, we measured the antidepressant-like effects of HNK in a rat model of chronic unpredictable mild stress (CUMS) and explored its possible mechanisms. The antidepressant-like effects of HNK were assessed in rats by an open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Then, serum levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) and hippocampal brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor α (GRα) levels were assessed to explore the possible mechanisms. We identified that HNK treatment (2, 4, and 8 mg/kg) alleviated the CUMS-induced behavioural deficits. Treatment with HNK also normalized the CUMS-induced hyperactivity of the limbic hypothalamic–pituitary–adrenal (HPA) axis, as indicated by reduced CRH, ACTH and CORT serum levels. In addition, HNK increased the expression of GRα (mRNA and protein) and BDNF (mRNA and protein) in the hippocampus. These data confirmed the antidepressant-like effects of HNK, which may be related to its normalizing the function of the HPA axis and increasing the BDNF level in the hippocampus.

Keywords

Honokiol Antidepressant Chronic unpredictable mild stress (CUMS) Brain-derived neurotrophic factor (BDNF) Hypothalamic–pituitary–adrenal (HPA) axis 

Notes

Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there are no conflicts of interest.

References

  1. 1.
    Bolton P, Wilk CM, Ndogoni L (2004) Assessment of depression prevalence in rural Uganda using symptom and function criteria. Soc Psychiatry Psychiatr Epidemiol 39:442–447CrossRefPubMedGoogle Scholar
  2. 2.
    Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B (2007) Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370:851–858CrossRefPubMedGoogle Scholar
  3. 3.
    Racagni G, Popoli M (2010) The pharmacological properties of antidepressants. Int Clin Psychopharmacol 25:117–131CrossRefPubMedGoogle Scholar
  4. 4.
    Sulakhiya K, Kumar P, Gurjar SS, Barua CC, Hazarika NK (2015) Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice. Pharmacol Biochem Behav 132:79–87CrossRefPubMedGoogle Scholar
  5. 5.
    Prasad R, Kappes JC, Katiyar SK (2016) Inhibition of NADPH oxidase 1 activity and blocking the binding of cytosolic and membrane-bound proteins by honokiol inhibit migratory potential of melanoma cells. Oncotarget 7:7899–7912PubMedPubMedCentralGoogle Scholar
  6. 6.
    Li WL, Zhao XC, Zhao ZW, Huang YJ, Zhu XZ, Meng RZ, Shi C, Yu L, Guo N (2016) In vitro antimicrobial activity of honokiol against Staphylococcus aureus in biofilm mode. J Asian Nat Prod Res 18:1178–1185CrossRefPubMedGoogle Scholar
  7. 7.
    Sulakhiya K, Kumar P, Jangra A, Dwivedi S, Hazarika NK, Baruah CC, Lahkar M (2014) Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice. Eur J Pharmacol 744:124–131CrossRefPubMedGoogle Scholar
  8. 8.
    Cheng YC, Hueng DY, Huang HY, Chen JY, Chen Y (2016) Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas. Oncotarget 7:29116–29130PubMedPubMedCentralGoogle Scholar
  9. 9.
    Wang X, Duan X, Yang G, Zhang X, Deng L, Zheng H, Deng C, Wen J, Wang N, Peng C, Zhao X, Wei Y, Chen L (2011) Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. PLoS ONE 6:e18490CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Qiang LQ, Wang CP, Wang FM, Pan Y, Yi LT, Zhang X, Kong LD (2009) Combined administration of the mixture of honokiol and magnolol and ginger oil evokes antidepressant-like synergism in rats. Arch Pharm Res 32:1281–1292CrossRefPubMedGoogle Scholar
  11. 11.
    Liu Y, Wang D, Yang G, Shi Q, Feng F (2016) Comparative pharmacokinetics and brain distribution of magnolol and honokiol after oral administration of Magnolia officinalis cortex extract and its compatibility with other herbal medicines in Zhi-Zi-Hou-Po Decoction to rats. Biomed Chromatogr 30:369–375CrossRefPubMedGoogle Scholar
  12. 12.
    Di Liberto V, Frinchi M, Verdi V, Vitale A, Plescia F, Cannizzaro C, Massenti MF, Belluardo N, Mudo G (2017) Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex. Psychopharmacology 234:559–573CrossRefPubMedGoogle Scholar
  13. 13.
    Amidfar M, Reus GZ, Quevedo J, Kim YK, Arbabi M (2017) Effect of co-administration of memantine and sertraline on the antidepressant-like activity and brain-derived neurotrophic factor (BDNF) levels in the rat brain. Brain Res Bull 128:29–33CrossRefPubMedGoogle Scholar
  14. 14.
    Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31:464–468CrossRefPubMedGoogle Scholar
  15. 15.
    Belvederi MM, Pariante C, Mondelli V, Masotti M, Atti AR, Mellacqua Z, Antonioli M, Ghio L, Menchetti M, Zanetidou S, Innamorati M, Amore M (2014) HPA axis and aging in depression: systematic review and meta-analysis. Psychoneuroendocrinology 41:46–62CrossRefGoogle Scholar
  16. 16.
    Le JJ, Yi T, Qi L, Li J, Shao L, Dong JC (2016) Electroacupuncture regulate hypothalamic-pituitary-adrenal axis and enhance hippocampal serotonin system in a rat model of depression. Neurosci Lett 615:66–71CrossRefPubMedGoogle Scholar
  17. 17.
    Bangsgaard EO, Ottesen JT (2017) Patient specific modeling of the HPA axis related to clinical diagnosis of depression. Math Biosci 287:24–35CrossRefPubMedGoogle Scholar
  18. 18.
    Salari AA, Fatehi-Gharehlar L, Motayagheni N, Homberg JR (2016) Fluoxetine normalizes the effects of prenatal maternal stress on depression- and anxiety-like behaviors in mouse dams and male offspring. Behav Brain Res 311:354–367CrossRefPubMedGoogle Scholar
  19. 19.
    Ge JF, Peng L, Cheng JQ, Pan CX, Tang J, Chen FH, Li J (2013) Antidepressant-like effect of resveratrol: involvement of antioxidant effect and peripheral regulation on HPA axis. Pharmacol Biochem Behav 114–115:64–69CrossRefPubMedGoogle Scholar
  20. 20.
    Jangra A, Dwivedi S, Sriram CS, Gurjar SS, Kwatra M, Sulakhiya K, Baruah CC, Lahkar M (2016) Honokiol abrogates chronic restraint stress-induced cognitive impairment and depressive-like behaviour by blocking endoplasmic reticulum stress in the hippocampus of mice. Eur J Pharmacol 770:25–32CrossRefPubMedGoogle Scholar
  21. 21.
    Jiang ML, Zhang ZX, Li YZ, Wang XH, Yan W, Gong GQ (2015) Antidepressant-like effect of evodiamine on chronic unpredictable mild stress rats. Neurosci Lett 588:154–158CrossRefPubMedGoogle Scholar
  22. 22.
    Li M, Fu Q, Li Y, Li S, Xue J, Ma S (2014) Emodin opposes chronic unpredictable mild stress induced depressive-like behavior in mice by upregulating the levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor. Fitoterapia 98:1–10CrossRefPubMedGoogle Scholar
  23. 23.
    Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391CrossRefPubMedGoogle Scholar
  24. 24.
    Katz RJ, Roth KA, Carroll BJ (1981) Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 5:247–251CrossRefPubMedGoogle Scholar
  25. 25.
    Bondi CO, Rodriguez G, Gould GG, Frazer A, Morilak DA (2008) Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology 33:320–331CrossRefPubMedGoogle Scholar
  26. 26.
    Kumar B, Kuhad A, Chopra K (2011) Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences. Psychopharmacology 214:819–828CrossRefPubMedGoogle Scholar
  27. 27.
    Jindal A, Mahesh R, Bhatt S (2013) Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level. Neurochem Int 63:465–475CrossRefPubMedGoogle Scholar
  28. 28.
    Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology 134:319–329CrossRefPubMedGoogle Scholar
  29. 29.
    Willner P (1991) Animal models as simulations of depression. Trends Pharmacol Sci 12:131–136CrossRefPubMedGoogle Scholar
  30. 30.
    Farhan M, Ikram H, Kanwal S, Haleem DJ (2014) Unpredictable chronic mild stress induced behavioral deficits: a comparative study in male and female rats. Pak J Pharm Sci 27:879–884PubMedGoogle Scholar
  31. 31.
    Pochwat B, Szewczyk B, Sowa-Kucma M, Siwek A, Doboszewska U, Piekoszewski W, Gruca P, Papp M, Nowak G (2014) Antidepressant-like activity of magnesium in the chronic mild stress model in rats: alterations in the NMDA receptor subunits. Int J Neuropsychopharmacol 17:393–405CrossRefPubMedGoogle Scholar
  32. 32.
    Patterson ZR, Ducharme R, Anisman H, Abizaid A (2010) Altered metabolic and neurochemical responses to chronic unpredictable stressors in ghrelin receptor-deficient mice. Eur J Neurosci 32:632–639CrossRefPubMedGoogle Scholar
  33. 33.
    de Angelis L (1990) The differential effects of post-session administration of amineptine and imipramine on memory processes in mice. Methods Find Exp Clin Pharmacol 12:23–27PubMedGoogle Scholar
  34. 34.
    Siegfried K, O’Connolly M (1986) Cognitive and psychomotor effects of different antidepressants in the treatment of old age depression. Int Clin Psychopharmacol 1:231–243CrossRefPubMedGoogle Scholar
  35. 35.
    Gupta D, Radhakrishnan M, Kurhe Y (2015) Effect of a novel 5-HT3 receptor antagonist 4i, in corticosterone-induced depression-like behavior and oxidative stress in mice. Steroids 96:95–102CrossRefPubMedGoogle Scholar
  36. 36.
    Holsboer F, Barden N (1996) Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocr Rev 17:187–205CrossRefPubMedGoogle Scholar
  37. 37.
    Wang M, Chen Q, Li M, Zhou W, Ma T, Wang Y, Gu S (2014) Alarin-induced antidepressant-like effects and their relationship with hypothalamus-pituitary-adrenal axis activity and brain derived neurotrophic factor levels in mice. Peptides 56:163–172CrossRefPubMedGoogle Scholar
  38. 38.
    Lin YT, Liu TY, Yang CY, Yu YL, Chen TC, Day YJ, Chang CC, Huang GJ, Chen JC (2016) Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation. Psychoneuroendocrinology 71:73–85CrossRefPubMedGoogle Scholar
  39. 39.
    Anacker C (2014) Adult hippocampal neurogenesis in depression: behavioral implications and regulation by the stress system. Curr Top Behav Neurosci 18:25–43CrossRefPubMedGoogle Scholar
  40. 40.
    Pan Y, Zhang WY, Xia X, Kong LD (2006) Effects of icariin on hypothalamic-pituitary-adrenal axis action and cytokine levels in stressed Sprague-Dawley rats. Biol Pharm Bull 29:2399–2403CrossRefPubMedGoogle Scholar
  41. 41.
    Cai L, Li R, Tang WJ, Meng G, Hu XY, Wu TN (2015) Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis. Eur Neuropsychopharmacol 25:1332–1341CrossRefPubMedGoogle Scholar
  42. 42.
    Gao X, Wang J, Yao H, Cai Y, Cheng R (2016) Serum BDNF concentration after delivery is associated with development of postpartum depression: a 3-month follow up study. J Affect Disord 200:25–30CrossRefPubMedGoogle Scholar
  43. 43.
    Liu WX, Wang J, Xie ZM, Xu N, Zhang GF, Jia M, Zhou ZQ, Hashimoto K, Yang JJ (2016) Regulation of glutamate transporter 1 via BDNF-TrkB signaling plays a role in the anti-apoptotic and antidepressant effects of ketamine in chronic unpredictable stress model of depression. Psychopharmacology 233:405–415CrossRefPubMedGoogle Scholar
  44. 44.
    Wang JM, Yang LH, Zhang YY, Niu CL, Cui Y, Feng WS, Wang GF (2015) BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress. Physiol Behav 151:360–368CrossRefPubMedGoogle Scholar
  45. 45.
    Huang EJ, Reichardt LF (2001) Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 24:677–736CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lu B, Nagappan G, Lu Y (2014) BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol 220:223–250CrossRefPubMedGoogle Scholar
  47. 47.
    Jornada LK, Moretti M, Valvassori SS, Ferreira CL, Padilha PT, Arent CO, Fries GR, Kapczinski F, Quevedo J (2010) Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain. J Psychiatr Res 44:506–510CrossRefPubMedGoogle Scholar
  48. 48.
    Schloesser RJ, Martinowich K, Manji HK (2012) Mood-stabilizing drugs: mechanisms of action. Trends Neurosci 35:36–46CrossRefPubMedGoogle Scholar
  49. 49.
    Thompson RM, Weickert CS, Wyatt E, Webster MJ (2011) Decreased BDNF, trkB-TK + and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci 36:195–203CrossRefGoogle Scholar
  50. 50.
    Sun J, Wang F, Hong G, Pang M, Xu H, Li H, Tian F, Fang R, Yao Y, Liu J (2016) Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress. Neurosci Lett 618:159–166CrossRefPubMedGoogle Scholar
  51. 51.
    Zhang Y, Gu F, Chen J, Dong W (2010) Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat. Brain Res 1366:141–148CrossRefPubMedGoogle Scholar
  52. 52.
    Li YC, Wang LL, Pei YY, Shen JD, Li HB, Wang BY, Bai M (2015) Baicalin decreases SGK1 expression in the hippocampus and reverses depressive-like behaviors induced by corticosterone. Neuroscience 311:130–137CrossRefPubMedGoogle Scholar
  53. 53.
    Yi LT, Li J, Li HC, Zhou Y, Su BF, Yang KF, Jiang M, Zhang YT (2012) Ethanol extracts from Hemerocallis citrina attenuate the decreases of brain-derived neurotrophic factor, TrkB levels in rat induced by corticosterone administration. J Ethnopharmacol 144:328–334CrossRefPubMedGoogle Scholar
  54. 54.
    Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W, Zink M, Hortnagl H, Flor H, Henn FA, Schutz G, Gass P (2005) Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 25:6243–6250CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacyShenzhen University General HospitalShenzhenChina
  2. 2.Department of PharmacyShenzhen Hospital, Southern Medical UniversityShenzhenChina
  3. 3.The Second People’s Hospital of China Three Gorges UniversityYichangChina

Personalised recommendations