Skip to main content
Log in

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice

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

Abstract

Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro−/anti-oxidative homeostasis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

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

  • An LJ, Guan S, Shi GF, Bao YM, Duan YL, Jiang B (2006) Protocatechuic acid from Alpiniaoxyphylla against MPP + −induced neurotoxicity in PC12 cells. Food Chem Toxicol 44:436–443

    Article  CAS  PubMed  Google Scholar 

  • Bettio LEB, Freitas AE, Neis VB, Santos DB, Ribeiro CM, Rosa RB (2014) Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress. Pharmacol Biochem Behav 127:7–14

    Article  CAS  PubMed  Google Scholar 

  • Budni J, Zomkowski AD, Engel D, Santos DB, dos Santos A, Moretti M et al (2013) Folic acid prevents depressive-like behavior and hippocampal antioxidant imbalance induced by restraint stress in mice. Exp Neurol 240:112–121

    Article  CAS  PubMed  Google Scholar 

  • Burri A, Maercker A, Krammer S, Simmen-Janevska K (2013) Childhood trauma and PTSD symptoms increase the risk of cognitive impairment in a sample of former indentured child laborers in old age. PLoS One 8:e57826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buynitsky T, Mostofsky DI (2009) Restraint stress in biobehavioral research: recent developments. Neurosci Biobehav Rev 7:1089–1098

    Article  Google Scholar 

  • Calabrese F, Molteni R, Riva, MA, (2011) Antistress properties of antidepressant drugs and their clinical implications Pharmacol Ther 132:39–56

  • Capra JC, Cunha MP, Machado DG, Zomkowski AD, Mendes BG, Santos AR, Pizzolatti MG, Rodrigues AL (2010) Antidepressant-like effect of scopoletin, a coumarin isolated from Polygala sabulosa (Polygalaceae) in mice: evidence for the involvement of monoaminergic systems. Eur J Pharmacol 643:232–238

    Article  CAS  PubMed  Google Scholar 

  • Christiansen SH, Olesen MV, Wortwein G, Woldbye DP (2011) Fluoxetine reverts chronic restrain stress induced depression like behavior and increase neuropeptide Y and galanin expression in mice. Behav Brain Res 216:585–591

    Article  CAS  PubMed  Google Scholar 

  • Chrousos GP (2009) Stress and disorders of stress system. Nat Rev Endocrinol 5:374–381

    Article  CAS  PubMed  Google Scholar 

  • Crupi R, Mazzon E, Marino A, La Spada G, Bramanti P, Cuzzocrea S, Spina E (2010) Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice. J Pineal Res 49:123–129

    CAS  PubMed  Google Scholar 

  • de Balk RS, Bridi JC, Portella Rde L, Carvalho NR, Dobrachinski F et al (2010) Clomipramine treatment and repeated restraint stress alter parameters of oxidative stress in brain regions of male rats. Neurochem Res 35:1761–1770

    Article  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–72

    Article  CAS  PubMed  Google Scholar 

  • Enache M, Van Waes V, Vinner E, Lhermitte M, Maccari S, Darnaudéry M (2008) Impact of an acute exposure to ethanol on the oxidative stress status in the hippocampus of prenatal restraint stress adolescent male rats. Brain Res 1191:55–62

    Article  CAS  PubMed  Google Scholar 

  • Fontella FU, Siqueira IR, Vasconcellos AP, Tabajara AR, Netto CA, Dalmaz C (2005) Repeated restraint stress induces oxidative damage in rat hippocampus. Neurochem Res 30:105–111

    Article  CAS  PubMed  Google Scholar 

  • Freitas AE, Bettio LEB, Neis VB, Santos DB, Ribeiro CM et al (2014) Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice. Prog Neuro-Psychopharmacol Biol Psych 50:143–150

    Article  CAS  Google Scholar 

  • Gold PW, Goodwin FK, Chrousos GP (1988) Clinical and biochemical manifestations of depression relation to the neurobiology of stress. N Engl J Med 319:413–420

    Article  CAS  PubMed  Google Scholar 

  • Guan S, Bao YM, Jiang B, An LJ (2006) Protective effect of protocatechuic acid from Alpiniaoxyphylla on hydrogen peroxide-induced oxidative PC12 cell death. Eur J Pharmacol 538:73–79

    Article  CAS  Google Scholar 

  • Hammen C, Kim EY, Eberhart NK (2009) Brennan PA, (2009) chronic and acute stress and the prediction of major depression in women. Depress Anxiety 26:718–723

    Article  PubMed  PubMed Central  Google Scholar 

  • Jaggi AS, Bhatia N, Kumar N, Anand P, Dhavan R (2011) A review on animal models for screening potential anti-stress agents. Neurol Sci 32:993–1005

    Article  PubMed  Google Scholar 

  • Jin P, Yu H, Tian-Lan, Zhang F, Quan Z (2015) Antidepressant-like effects of Oleoylethanolamide in a mouse model of chronic unpredictable mild stress. Pharmacol Biochem Behav 133:146–154

  • Jindal A, Mahesh R, Bhatt S (2013) Etazolate, a phosphodiesterase 4 inhibitor reverses chronic unpredictable mild stress-induced depression-like behavior and brain oxidative damage. Pharmacol Biochem Behav 105:63–70

    Article  CAS  PubMed  Google Scholar 

  • Kalueff AV, Wheaton M, Murphy DL (2007) What’s wrong with my mouse model? Advances and strategies in animal modeling of anxiety and depression. Behav Brain Res 179:1–18

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Kim GH, Hwang KH (2012) Monoamine oxidase and dopamine b-hydroxylase inhibitors from the fruits of Gardenia jasminoides. Biomol Ther 20:214–219

    Article  CAS  Google Scholar 

  • Kobayashi N, Machida T, Takahashi T, Takatsu H, Shinkai T, Abe K et al (2009) Elevation by oxidative stress and aging of hypothalamic-pituitary-adrenal activity in rats and its prevention by vitamin. Eur J Clin Biochem Nutr 45:207–213

    Article  CAS  Google Scholar 

  • Kumar A, Goyal R (2008) Quercetin protects against acute immobilization stress-induced behavior and biochemical alterations in mice. J Med Food 11:469–473

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Garg R, Gaur V, Kumar P (2009) Nitric oxide mechanism in protective effect of imipramine and venlafaxine against acute immobilization stress induced behavioral and biochemical alteration in mice. Neurosci Lett 467:72–75

    Article  CAS  PubMed  Google Scholar 

  • Lang UE, Borgwardt S (2013) Molecular mechanism of depression: perspective on new treatment strategies. Cell Physiol Biochem 31:761–777

    Article  CAS  PubMed  Google Scholar 

  • Lee AL, Ogle WO, Sapolsky RM (2002) Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord 4:117–128

    Article  CAS  PubMed  Google Scholar 

  • Lee B, Shim I, Lee HJ, Yang Y, Hahm DH (2009) Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats. Neurosci Lett 453:151–156

    Article  CAS  PubMed  Google Scholar 

  • Lin WL, Hsieh YJ, Chou FP, Wang CJ, Cheng MT, Tseng TH (2003) Hibiscus protocatechuic acid inhibits lipopolysaccharide-induced rat hepatic damage. Arch Toxicol 77:42–47

    Article  CAS  PubMed  Google Scholar 

  • Lovell MA, Xie C, Markesbery WR (1998) Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease. Neurol 51:1562–1566

    Article  CAS  Google Scholar 

  • Mao QQ, Huang Z, Zhong XM, Xian YF, Ip SP (2014) Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice. Neurochem Int 74:36–41

    Article  CAS  PubMed  Google Scholar 

  • Mazure CM (1998) Life stressor as risk factors in depression. Clin Psychol Sci Pract 5:291–295

    Article  Google Scholar 

  • McKinnon MC, Yucel K, Nazarov A, MacQueen GM (2009) A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci 34:41–54

    PubMed  PubMed Central  Google Scholar 

  • Mishra HP, Fridovich I (1972) Role of superoxide anion in auto-oxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175

    Google Scholar 

  • Moretti M, Budni J, Dos Santos DB, Antunes A, Daufenbach JF, Manosso LM (2013) Protective effects of ascorbic acid on behavior and oxidative staturs of restrint-stressed mice. J Mol Neurosci 49:68–79

    Article  CAS  PubMed  Google Scholar 

  • Morris MC, Compas BE, Garber J (2012) Relations among posttraumatic stress disorder, comorbid major depression, and HPA function: a systematic review and meta-analysis. Clin Psychol Rev 32:301–315

    Article  PubMed  PubMed Central  Google Scholar 

  • Muley MM, Thakare VN, Patil RR, Kshirsagar AD, Naik SR (2012) Silymarin improves the behavioral, biochemical and histoarchitecture alterations in focal ischemic rats: comparative evaluation with piracetam and protocatachuic acid. Pharmacol Biochem Behav 102:286–293

    Article  CAS  PubMed  Google Scholar 

  • Muley MM, Thakare VN, Patil RR, Bafna PA, Naik SR (2013) Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model. Life Sci 93:51–57

    Article  CAS  PubMed  Google Scholar 

  • Naik SR, Thakare VN, Patil SR (2011) Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property. Exp Toxicol Pathol 63:419–431

    Article  CAS  PubMed  Google Scholar 

  • Niki E (2012) Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products? FEBS Lett 586:767–770

    Article  Google Scholar 

  • Ohkawa H, Nobuko K (1979) Assay of lipid peroxide in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  • Ostadhadi S, Imran Khan M, Norouzi-Javidan A, Dehpour AR (2016) Antidepressant effect of pramipexole in mice forced swimming test: a cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway. Biomed Pharmacother 81:295–304

    Article  CAS  PubMed  Google Scholar 

  • Pacheco-Palencia LA, Mertens-Talcott S, Talcott ST (2008) Chemical composition, antioxidant properties, and thermal stability of phytochemical enriched oil from acai (Euterpeoleracea Mart). J Agric Food Chem 56:4631–4636

    Article  CAS  PubMed  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    CAS  PubMed  Google Scholar 

  • Rang HP, Dale MM, Ritter JM, Flower RJ (2007) Selective serotonin reuptake inhibitors pharmacology, pp 566 Churchill Livingstone. Publication, Elsevier

    Google Scholar 

  • Ressler KJ, Nemeroff CB (2000) Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety 12(S1):2–19

    Article  PubMed  Google Scholar 

  • Rodrigues ALS, Rocha JB, Mello CF, Souza DO (1996) Effect of perinatal lead exposure on rat behavior in open-field and two-way avoidance tasks. Pharmacol Toxicol 79:150–156

    Article  CAS  PubMed  Google Scholar 

  • Rosa JM, Dafre AL, Rodrigues AL (2013) Antidepressant like responses in the forced swimming test elicited by glutathione and redox modulation. Behav Brain Res 253:165–172

    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. Humanist Psychol 22:67–73

    CAS  Google Scholar 

  • Shi GF, An LJ, Jiang B, Guan SI, Bao YM (2006) Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo. Neurosci Lett 403:206–210

    Article  CAS  PubMed  Google Scholar 

  • Thakare VN, Patel BM (2015) Potential targets for the development of novel antidepressants: future perspectives. CNS Neurol Disord Drug Targets 14:270–281

    Article  CAS  PubMed  Google Scholar 

  • Thakare VN, Dhakane VD, Patel BM (2016) Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus. Pharmacol Rep 68:1020–1027

    Article  CAS  PubMed  Google Scholar 

  • Zafir A, Banu N (2007) Antioxidant potential of fluoxetine in comparision to Curcuma longa in restrint-stressed rats. Eur J Pharmacol 572:23–31

    Article  CAS  PubMed  Google Scholar 

  • Zafir A, Ara A, Banu N (2009) In vivo antioxidant status: a putative target for antidepressant action. Prog Neuro-Psychopharmacol Biol Psychiatry 33:220–228

    Article  CAS  Google Scholar 

  • Zhang YJ, Wu L, Zhang QL, Li J, Yin FX, Yuan Y (2011) Pharmacokinetics of phenolic compounds of Danshen extract in rat blood and brain by microdialysis sampling. J Ethnopharmacol 136:129–136

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Li G, Szeto S, Chong C, Quan Q et al (2015) Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson's disease. Free Radic Biol Med 84:331–333

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Xie W, Dai J, Wang Z, Huang Y (2009) The varying effects of short-term and long-term corticosterone injections on depression-like behavior in mice. Brain Res 1261:82–90

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors are grateful to Prof. M. N. Navale, Founder President, Sinhgad Technical Education Society, Dr. R. N. Kane, Principal, and Rajesh R Patil, Sinhgad Institute of Pharmaceutical Sciences for providing necessary facilities, encouragement and support in the completion of present research studies.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bhoomika M. Patel.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thakare, V.N., Dhakane, V.D. & Patel, B.M. Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice. Metab Brain Dis 32, 401–413 (2017). https://doi.org/10.1007/s11011-016-9922-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-016-9922-y

Keywords

Navigation