Skip to main content
SpringerLink
Log in

Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

An Erratum to this article was published on 26 October 2015

Abstract

Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abdel-Wahab B, Salama RH (2011) Venlafaxine protects against stress induced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharmacol Biochem Behav 100:59–65

    Article  CAS  PubMed  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  • Antony JM, van Marle G, Opii W, Butterfield A, Mallet F, Yong VW, Wallace JL, Deacon RN, Warren K, Power C (2004) Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci 7:1088–1095

    Article  CAS  PubMed  Google Scholar 

  • Bai F, Li X, Clay M, Lindstrom T, Skolnick P (2001) Intra and interstrain differences in models of “behavioral despair”. Pharmacol Biochem Behav 70:187–192

    Article  CAS  PubMed  Google Scholar 

  • Behr GA, Moreira JCF, Frey BN (2012) Preclinical and clinical evidence of antioxidant effects of antidepressant agents: implications for the pathophysiology of major depressive disorder. Oxidative Med Cell Longev. doi:10.1155/2012/609421

    Google Scholar 

  • Berton O, Nestler EJ (2006) New approaches to antidepressant discovery: beyond monoamines. Neuroscience 7:137–151

    CAS  PubMed  Google Scholar 

  • Bilici M, Efe H, Koroglu MA, Uydu HA, Bekaroglu M, Deger O (2001) Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 64:43–51

    Article  CAS  PubMed  Google Scholar 

  • Cheetham SC, Heal DJ (2000) Antidepressant and anxiolytic drugs. In: Bittar EE, Bittar N (eds) Biological Psychiatry. JAI Press, Stanford, CT, p 551–567

  • Chen J, Lin D, Zhang C, Gaowen L, Zhang N, Ruan L, Yan Q, Li J et al (2015) Antidepressant-like effect of ferulic acid: involvement of serotonergic and norepinergic systems. Metab Brain Dis 30:129–136

    Article  CAS  PubMed  Google Scholar 

  • Cheng Y, Yang S, Yang K, Chen M, Lin F (2011) The effects of ferulic acid on nucleus pulposus cells under hydrogen peroxide-induced oxidative stress. Process Biochem 46:1670–1677

    Article  CAS  Google Scholar 

  • Cunha MP, Machado DG, Bettio LEB, Capra JC, Rodrigues ALS (2008) Interaction of zinc with antidepressants in the tail suspension test. Prog Neuro-Psychopharmacol Biol Psychiatry 32:1913–1920

    Article  CAS  Google Scholar 

  • Felipe FCB, Sousa Filho JT, Souza LEO, Silveira JA, Uchoa DEA, Silveira ER et al (2007) Piplartine, an amide alkaloid from Piper tuberculatum, presents anxiolytic and antidepressant effects in mice. Phytomedicine 14:605–612

    Article  CAS  Google Scholar 

  • Graf E (1992) Antioxidant potential of ferulic acid. Free Radic Biol Med 13:435–448

    Article  CAS  PubMed  Google Scholar 

  • Harro J, Kanarika M, Kaart T, Matrov D, Kõiv K, Mällo T et al (2014) Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain. Behav Brain Res 267:83–94

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto K, Sawa A, Iyo M (2007) Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 62:1310–1316

    Article  CAS  PubMed  Google Scholar 

  • Herken H, Gurel A, Selek S, Armutcu F, Ozen ME, Bulut M et al (2007) Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment. Arch Med Res 38:247–252

    Article  CAS  PubMed  Google Scholar 

  • Hill MN, Hellemans KGC, Vermad P, Gorzalka BB, Weinberg J (2012) Neurobiology of chronic mild stress: parallels to major depression. Neurosci Biobehav Rev 36:2085–2117

    Article  CAS  PubMed  Google Scholar 

  • Inkielewicz-Stêpniak I (2011) Impact of fluoxetine on liver damage in rats. Pharmacol Rep 63:441–447

    Article  PubMed  Google Scholar 

  • Itagaki S, Kurokawa T, Nakata C, Saito Y, Oikawa S, Kobayashi M et al (2009) In vitro and in vivo antioxidant properties of ferulic acid: a comparative study with other natural oxidation inhibitors. Food Chem 114:466–471

    Article  CAS  Google Scholar 

  • Laaksonen DE, Atalay M, Niskanen L, Uusitupa M, Hänninen O et al (1999) Blood glutathione homeostasis as a determinant of resting and exercise-induced oxidative stress in young men. Redox Rep 4:53–59

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Han C, Patkar AA, Masand PS, Pae C (2013) Oxidative/nitrosative stress and antidepressants: targets for novel antidepressants. Prog Neuro-Psychopharmacol Biol Psychiatry 46:224–235

    Article  CAS  Google Scholar 

  • Liu X, Liu F, Yue R, Li Y, Zhang J, Wang S et al (2013) The antidepressant-like effect of bacopaside I: possible involvement of the oxidative stress system and the noradrenergic system. Pharmacol Biochem Behav 110:224–230

    Article  CAS  PubMed  Google Scholar 

  • Lobato KR, Cardoso CC, Binfaré RW, Budni J, Wagner CLR, Brocardo PS et al (2010) Tocopherol administration produces an antidepressant-like effect in predictive animal models of depression. Behav Brain Res 209:249–259

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Lucca G, Comima CM, Valvassori SS, Réus GZ, Vuolo F, Petronilho F et al (2009) Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochem Int 54:358–362

    Article  CAS  PubMed  Google Scholar 

  • Maes M, Galecki P, Chang YS, Berk M (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 35:676–692

    Article  CAS  PubMed  Google Scholar 

  • Mancuso C, Santangelo R (2014) Ferulic acid: pharmacological and toxicological aspects. Food Chem Toxicol 65:185–195

    Article  CAS  PubMed  Google Scholar 

  • Marklund SL (1985) Pyrogallol autoxidation. In: Greenwald RA (ed) Handbook for oxygen radical research. CRC Press, Boca Raton, pp 243–247

    Google Scholar 

  • Maurya D, Devasagayam T (2010) Antioxidant and prooxidant nature of hydroxycinnamic acid derivatives ferulic and caffeic acids. Food Chem Toxicol 48:3369–3373

    Article  CAS  PubMed  Google Scholar 

  • Moretti M, Colla A, Balen GO, dos Santos DB, Budni J, de Freitas AE et al (2011) Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress. J Psychiatr Res 46:331–340

    Article  PubMed  Google Scholar 

  • Moylan S, Berka M, Deana OM, Samunia Y, Williams LJ, O’Neila A et al (2014) Oxidative & nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev 45:46–62

    Article  CAS  PubMed  Google Scholar 

  • Niki E (2012) Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products? FEBS Lett 586:3767–3770

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  • Pandya CD, Howell KR, Pillai A (2013) Antioxidants as potential therapeutics for neuropsychiatric disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 46:214–223

    Article  CAS  Google Scholar 

  • Pilkington PD, Reavley NJ, Jorma AF (2013) The Australian public’s beliefs about the causes of depression: associated factors and changes over 16 years. J Affect Disord 150:356–362

    Article  PubMed  Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues AF, Roecker R, Junges GM, Lima DD, Cruz JGP, Wyse ATS et al (2014) Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol. Cell Biochem Funct 32:387–394

    Article  CAS  PubMed  Google Scholar 

  • Roy S, Metya SK, Sannigrahi S, Rahaman N, Ahmed F (2013) Treatment with ferulic acid to rats with streptozotocin-induced diabetes: effects on oxidative stress, pro-inflammatory cytokines, and apoptosis in the pancreatic B cell. Endocrine 44:369–379

    Article  CAS  PubMed  Google Scholar 

  • Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S (2007) Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative—antioxidative systems. Hum Psychopharmacol Clin 22:67–73

    Article  CAS  Google Scholar 

  • Scapagnini G, Davinelli S, Drago F, De Lorenzo A, Oriani G (2012) Antioxidants as antidepressants: fact or fiction? CNS Drugs 26:477–490

    Article  CAS  PubMed  Google Scholar 

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370

    Article  CAS  PubMed  Google Scholar 

  • Tikhonova MA, Kulikov AV, Bazovkina DV, Morozova MV, Naumenko VS, Popova MK (2012) Antidepressant-like effects of central BDNF administration in mice of antidepressant sensitive catalepsy (ASC) strain. Chin J Physiol 55:284–293

    CAS  PubMed  Google Scholar 

  • Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333

    Article  CAS  PubMed  Google Scholar 

  • Willner P, Scheel-Krügerb J, Belzung C (2013) The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 37:2331–2371

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Xiao H, Zhao J, Zhao T (2012) Cardioprotective effect of sodium ferulate in diabetic rats. Int J Med Sci 9:291–300

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yabe T, Hirahara H, Harada N, Ito N, Nagai T, Sanagi T et al (2010) Ferulic acid induces neural progenitor cell proliferation in vitro and in vivo. Neuroscience 165:515–524

    Article  CAS  PubMed  Google Scholar 

  • Yu L, Zhang Y, Ma R, Bao L, Fang J, Yu T (2006) Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. Eur Neuropsychopharmacol 16:170–177

    Article  CAS  PubMed  Google Scholar 

  • Zeni ALB (2014) Multiple biological effects of Ferulic acid: focus on promising antidepressant benefits. In: Warren B (ed) Ferulic acid: antioxidant properties, uses and potential health benefits. Nova Science Publishers, Inc., New York, pp 71–92

    Google Scholar 

  • Zeni ALB, Zomkowski ADE, Dal-Cim T, Maraschin M, Rodrigues ALS, Tasca CI (2011) Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway. J Ethnopharmacol 137:864–874

    Article  PubMed  Google Scholar 

  • Zeni ALB, Zomkowski ADE, Maraschin M, Rodrigues ALS, Tasca CL (2012) Ferulic acid exerts antidepressant-like effect in the tail suspension test in mice: evidence for the involvement of the serotonergic system. Eur J Pharmacol 679:68–74

    Article  CAS  PubMed  Google Scholar 

  • Zeni ALB, Vandresen-Filho S, Dal-Cim T, Martins WC, Bertoldo DB, Maraschin M et al (2014) Aloysia gratissima prevents cellular damage induced by glutamatergic excitotoxicity. J Pharm Pharmacol 66:1294–1302

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Huanga X, Wang Y, Xiea Y, Qiu X, Ren P et al (2011) Ferulic acid-induced anti-depression and prokinetics similar to Chaihu–Shugan–San via polypharmacology. Brain Res Bull 86:222–228

    Article  CAS  PubMed  Google Scholar 

  • Zhao Z, Moghadasian MH (2008) Chemistry, natural sources, dietary intake and pharmacokinetic properties of ferulic acid: a review. Food Chem 109:691–702

    Article  CAS  PubMed  Google Scholar 

  • Zomkowski ADE, Engel D, Gabilan NH, Rodrigues ALS (2010) Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. Eur Neuropsychopharmacol 20:793–801

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Universidade Regional de Blumenau (FURB) and Programa Institucional de Bolsas de Iniciação Científica (PIBIC) - Conselho Nacional de Pesquisa (CNPq) scholarships. The authors thank the English review of Marta Helena Caetano (FURB).

Author information

Authors and Affiliations

  1. Laboratório de Análise de Substâncias Bioativas, Departamento de Ciências Naturais, Universidade Regional de Blumenau, Campus I, Blumenau, 89012-900, Santa Catarina, Brazil

    Juliana Lenzi, Adriana de Sousa Rós, Bianca Blanski de Castro & Ana Lúcia Bertarello Zeni

  2. Laboratório de Fisiologia, Departamento de Ciências Naturais, Universidade Regional de Blumenau, Blumenau, 89012900, Santa Catarina, Brazil

    Andre Felipe Rodrigues & Débora Delwing Dal Magro

  3. Departamento de Medicina, Universidade da Região de Joinville, Joinville, 89219-710, Santa Catarina, Brazil

    Daniela Delwing de Lima

Authors
  1. Juliana Lenzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre Felipe Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adriana de Sousa Rós
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bianca Blanski de Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniela Delwing de Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Débora Delwing Dal Magro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Lúcia Bertarello Zeni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Lúcia Bertarello Zeni.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lenzi, J., Rodrigues, A.F., Rós, A.d.S. et al. Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system. Metab Brain Dis 30, 1453–1463 (2015). https://doi.org/10.1007/s11011-015-9725-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-015-9725-6

Keywords

Search

Navigation