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Enriched Flavonoid Fraction from Cecropia pachystachya Trécul Leaves Exerts Antidepressant-like Behavior and Protects Brain Against Oxidative Stress in Rats Subjected to Chronic Mild Stress

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Abstract

The purpose of this study was to assess the effect of an enriched C-glycosyl flavonoids fraction (EFF-Cp) from Cecropia Pachystachya leaves on behavior, mitochondrial chain function, and oxidative balance in the brain of rats subjected to chronic mild stress. Male Wistar rats were divided into experimental groups (saline/no stress, saline/stress, EFF-Cp/no stress, and EFF-Cp/stress). ECM groups were submitted to stress for 40 days. On the 35th ECM day, EFF-Cp (50 mg/kg) or saline was administrated and the treatments lasted until the 42nd day. On the 41st and 42nd days, the animals were submitted to the splash test and the forced swim test. After these behavioral tests, the enzymatic activity of mitochondrial chain complexes and oxidative stress were analyzed. EFF-Cp reversed the depressive-like behavior induced by ECM. It also reversed the increase in thiobarbituric acid reactive species, myeloperoxidase activity, and nitrite/nitrate concentrations in some brain regions. The reduced activities of the antioxidants superoxide dismutase and catalase in some brain regions were also reversed by EFF-Cp. The most pronounced effect of EFF-Cp on mitochondrial complexes was an increase in complex IV activity in all studied regions. Thus, it is can be concluded that EFF-Cp exerts an antidepressant-like effect and that oxidative balance may be an important physiological process underlying these effects.

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References

  • Abelaira HM, Réus GZ, Ribeiro KF, Zappellini G, Ferreira GK, Gomes LM, Carvalho-Silva M, Luciano TF, Marques SO, Streck EL, Souza CT, Quevedo J (2011) Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats. Neurochem Int 59:1163–1174

    Article  CAS  PubMed  Google Scholar 

  • Abelaira HM, Réus GZ, Ribeiro KF, Steckert AV, Mina F, Rosa DV et al (2013) Effects of lamotrigine on behavior, oxidative parameters and signaling cascades in rats exposed to the chronic mild stress model. Neurosci Res 75:324–330

    Article  CAS  PubMed  Google Scholar 

  • Adzic M, Djordjevic A, Demonacos C, Krstic-Demonacos M, Radojcic MB (2009) The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats. Int J Biochem Cell Biol 41:2181–2188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Agostinho FR, Scaini G, Ferreira GK, Jeremias IC, Réus GZ, Rezin GT et al (2009) Effects of olanzapine, fluoxetine and olanzapine/fluoxetine on creatine kinase activity in rat brain. Brain Res Bull 80:337–340

    Article  CAS  PubMed  Google Scholar 

  • Amikishieva AV, Ilnitskaya SI, Nikolin VP, Popova NA, Kaledin VI (2011) Depressive-like psychoemotional state versus acute stresses enhances Lewis lung carcinoma metastasis in C57BL/6J mice. Exp Oncol 33:222–225

    CAS  PubMed  Google Scholar 

  • Andrade-Cetto A, Heinrich M (2005) Mexican plants with hypoglycaemic effect used in the treatment of diabetes. J Ethnopharmacol 99:325–348

    Article  PubMed  Google Scholar 

  • Arent CO, Réus GZ, Abelaira HM, Ribeiro KF, Steckert AV, Mina F et al (2012) Synergist effects of n-acetylcysteine and deferoxamine treatment on behavioral and oxidative parameters induced by chronic mild stress in rats. Neurochem Int 61:1072–1080

    Article  CAS  PubMed  Google Scholar 

  • Bakunina N, Pariante CM, Zunszain PA (2015) Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology [Epub ahead of print]

  • Bannister JV, Calabrese L (1987) Assays for superoxide dismutase. Methods Biochem Anal 32:279–312

    Article  CAS  PubMed  Google Scholar 

  • Barinaga M (1997) What makes brain neurons run? Science 276:196–198

    Article  CAS  PubMed  Google Scholar 

  • Behr GA, Moreira JC, Frey BN (2012) Preclinical and clinical evidence of antioxidant effects of antidepressant agents: implications for the pathophysiology of major depressive disorder Oxid Med Cell Longev 2012, 609421

  • Belmaker RH, Agam G (2008) Major depressive disorder. N Engl J Med 358:55–68

    Article  CAS  PubMed  Google Scholar 

  • Berg CC, Rosselli PF (2005) Cecropia. Flora Neotropica/The New York Botanical Garden, New York

    Google Scholar 

  • Bhat AH, Dar KB, Anees S, Zargar MA, Masood A, Sofi MA, Ganie AS (2015) Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 74:101–110

    Article  CAS  PubMed  Google Scholar 

  • Bhatia N, Jaggi AS, Singh N, Anand P, Dhawan R (2011) Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis. Nat Med 65:532–543

    Article  CAS  Google Scholar 

  • Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O (2012) Oxidative stress and antioxidant defense. World Allergy Organ J5:9–19

    Article  Google Scholar 

  • Brines M, Cerami A (2006) Discovering erythropoietin’s extra-hematopoietic functions: biology and clinical promise. Kidney Int 70:246–250

    Article  CAS  PubMed  Google Scholar 

  • Brown GC, Cooper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356:295–298

    Article  CAS  PubMed  Google Scholar 

  • Byun J, Henderson JP, Mueller DM, Heinecke JW (1999) 8-Nitro-2′-deoxyguanosine, a specific marker of oxidation by reactive nitrogen species, is generated by the myeloperoxidase-hydrogen peroxide-nitrite system of activated human phagocytes. Biochemistry 38:2590–2600

    Article  CAS  PubMed  Google Scholar 

  • Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM (2007) Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8:766–775

    Article  CAS  PubMed  Google Scholar 

  • Calabrese F, Molteni R, Racagni G, Riva MA (2009) Neuronal plasticity: a link between stress and mood disorders. Psychoneuroendocrinology 1:S208–S216

    Article  Google Scholar 

  • Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316

    Article  CAS  PubMed  Google Scholar 

  • Chaillou LL, Nazareno MA (2006) New method to determine antioxidant activity of polyphenols. J Agric Food Chem 54:8397–8402

    Article  CAS  PubMed  Google Scholar 

  • Che Y, Zhou Z, Shu Y, Zhai C, Zhu Y, Gong S et al (2015) Chronic unpredictable stress impairs endogenous antioxidant defense in rat brain. Neurosci Lett 584:208–213

    Article  CAS  PubMed  Google Scholar 

  • Costa GM, Ortmann CF, Schenkel EP, Reginatto FH (2011a) An HPLC-DAD method to quantification of main phenolic compounds from leaves of Cecropia Species. J Braz Chem Soc 22:1096–1102

    Article  CAS  Google Scholar 

  • Costa GM, Schenkel EP, Reginatto FH (2011b) Chemical and pharmacological aspects of the genus Cecropia. Nat Prod Commun 6:913–920

    CAS  PubMed  Google Scholar 

  • Dalle-Donne I, Aldini G, Carini M, Colombo R, Rossi R, Milzani A (2006) Protein carbonylation, cellular dysfunction, and disease progression. J Cell Mol Med 10:389–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Mello AH, Gassenferth A, Schraiber RB, Souza LR, Florentino D, Danielski LG et al (2014) Effects of omega-3 on behavioral and biochemical parameters in rats submitted to chronic mild stress. Metab Brain Dis 29:691–699

    Article  PubMed  Google Scholar 

  • De Young LM, Kheifets JB, Ballaron SJ, Young JM (1989) Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents. Agents Actions 26:335–341

    Article  PubMed  Google Scholar 

  • Deepha V, Praveena R, Sivakumar R, Sadasivam K (2014) Experimental and theoretical investigations on the antioxidant activity of isoorientin from Crotalaria globosa. Spectrochim Acta A Mol Biomol Spectrosc 121:737–745

    Article  CAS  PubMed  Google Scholar 

  • Dhir A, Kulkarni SK (2007) Involvement of l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of venlafaxine in mice. Prog Neuropsychopharmacol Biol Psychiatry 31:921–925

    Article  CAS  PubMed  Google Scholar 

  • El-Alfy AT, Abourashed EA, Matsumoto rr (2012) Nature against depression. Curr Med Chem 19:2229–2241

    Article  CAS  PubMed  Google Scholar 

  • Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421

    Article  CAS  PubMed  Google Scholar 

  • Fedorova M, Bollineni RC, Hoffmann R (2014) Protein carbonylation as a major hallmark of oxidative damage: update of analytical strategies. Mass Spectrom Rev 33:79–97

    Article  CAS  PubMed  Google Scholar 

  • Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM et al (1995) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–26

    Article  Google Scholar 

  • Gamaro GD, Streck EL, Matté C, Prediger ME, Wyse AT, Dalmaz C (2003) Reduction of hippocampal Na+, K+-ATPase activity in rats subjected to an experimental model of depression. Neurochem Res 28:1339–1344

    Article  CAS  PubMed  Google Scholar 

  • Gao J, Chi ZF, Liu XW, Shan PY, Wang R (2007) Mitochondrial dysfunction and ultrastructural damage in the hippocampus of pilocarpine-induced epileptic rat. Neurosci Lett 411:152–157

    Article  CAS  PubMed  Google Scholar 

  • Garabadu D, Ahmad A, Krishnamurthy S (2015) Risperidone attenuates modified stress-re-stress paradigm-induced mitochondrial dysfunction and apoptosis in rats exhibiting post-traumatic stress disorder-like symptoms. J Mol Neurosci Mar 7. Epub ahead of print. doi: 10.1007/s12031-015-0532-7

  • Garcia LS, Comim CM, Valvassori SS, Réus GZ, Andreazza AC, Stertz L et al (2008) Chronic administration of ketamine elicits antidepressant-like effects in rats without affecting hippocampal brain-derived neurotrophic factor protein levels. Basic Clin Pharmacol Toxicol 103:502–506

    Article  CAS  PubMed  Google Scholar 

  • Gazal M, Ortmann CF, Martins FA, Streck EL, Quevedo J, de Campos AM et al (2014) Antidepressant-like effects of aqueous extract from Cecropiapachystachya leaves in a mouse model of chronic unpredictable stress. Brain Res Bull 108:10–17

    Article  PubMed  Google Scholar 

  • Ghezzi D, Zeviani M (2012) Assembly factors of human mito-chondrial respiratory chain complexes: physiology and pathophysiology. Adv Exp Med Biol 748:65–66

    Article  CAS  PubMed  Google Scholar 

  • Gibson SA, Korade Ž, Shelton RC (2012) Oxidative stress and glutathione response in tissue cultures from persons with major depression. J Psychiatr Res 46:1326–1332

    Article  PubMed  PubMed Central  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15 N]nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  • Green PS, Mendez AJ, Jacob JS, Crowley JR, Growdon W, Hyman BT et al (2004) Neuronal expression of myeloperoxidase is increased in Alzheimer’s disease. J Neurochem 90:724–733

    Article  CAS  PubMed  Google Scholar 

  • Harrison JE, Schultz J (1976) Studies on the chlorinating activity of myeloperoxidase. J Biol Chem 251:1371–1374

    CAS  PubMed  Google Scholar 

  • Hughes BP (1962) A method for estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathologic sera. Clin Chim Acta 7:597–604

    Article  CAS  PubMed  Google Scholar 

  • Ignácio ZM, Réus GZ, Abelaira HM, Quevedo J (2014) Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression. Neuroscience 275:455–468

    Article  PubMed  Google Scholar 

  • Isingrini E, Camus V, Le Guisquet AM, Pingaud M, Devers S, Belzung C (2010) Association between repeated unpredictable chronic mild stress (UCMS) procedures with a high fat diet: a model of fluoxetine resistance in mice. PLoS ONE 5:e10404

    Article  PubMed  PubMed Central  Google Scholar 

  • Jou SH, Chiu NY, Liu CS (2009) Mitochondrial dysfunction and psychiatric disorders. Chang Gung Med J32:370–379

    Google Scholar 

  • Lee SY, Lee SJ, Han C, Patkar AA, Masand PS, Pae CU (2013) Oxidative/nitrosative stress and antidepressants: targets for novel antidepressant. Prog Neuropsychopharmacol Biol Psychiatry 46:224–235

    Article  CAS  PubMed  Google Scholar 

  • Leuchter AF, Cook IA, Hamilton SP, Narr KL, Toga A, Hunter AM et al (2010) Biomarkers to predict antidepressant response. Curr Psychiatry Rep 12:553–562

    Article  PubMed  PubMed Central  Google Scholar 

  • Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG et al (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

    Article  CAS  PubMed  Google Scholar 

  • Liang HL, Ongwijitwat S, Wong-Riley MT (2009) The role of phosphorylated glucocorticoid receptor in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats. Int J Biochem Cell Biol 41:2181–2188

    Article  Google Scholar 

  • Liu Y, Lan N, Ren J, Wu Y, Wang ST, Huang XF et al (2015) Orientin improves depression-like behavior and BDNF in chronic stressed mice. Mol Nutr Food Res. doi:10.1002/mnfr.201400753

    Google Scholar 

  • Lowry OH, Rosebough NG, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Lucca G, Comim 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 

  • Madrigal JL, Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Rodrigo J et al (2001) Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 24:420–429

    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 

  • Manji H, Kato T, Di Prospero NA, Ness S, Beal MF, Krams M et al (2012) Impaired mitochondrial function in psychiatric disorders. Nat Rev Neurosci 13:293–307

    CAS  PubMed  Google Scholar 

  • Morris G, Berk M (2015) The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med 13:68

    Article  PubMed  PubMed Central  Google Scholar 

  • Moylan S, Maes M, Wray NR, Berk M (2013) The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Mol Psychiatry 18(5):595–606

    Article  CAS  PubMed  Google Scholar 

  • Mu HN, Li Q, Pan CS, Liu YY, Yan L, Hu BH et al (2015) Caffeic acid Attenuates rat liver reperfusion injury through Sirt3-dependent regulation of mitochondrial respiratory chain. Free Radic Biol Med. doi:10.1016/j.freeradbiomed.2015.04.033

    PubMed  Google Scholar 

  • Mutlu O, Gumuslu E, Ulak G, Celikyurt IK, Kokturk S, Kır HM et al (2012) Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice. Life Sci 91:1252–1262

    Article  CAS  PubMed  Google Scholar 

  • Nicasio-Torres MP, Erazo-Gómez JC, Cruz-Sosa F (2009) In vitro propagation of two antidiabetic species known as guarumbo: Cecropiaobtusifolia and Cecropiapeltata. Acta Physiol Plantarum 31:905–914

    Article  Google Scholar 

  • Pacheco NR, Pinto NCC, Silva JM, Mendes RF, Costa JC, Aragão DMO, Castañon MCMN, Scio E (2014) Cecropiapachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects. BioMed Res Int 2014:1–10

    Article  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain: stereotaxic coordinates, 2nd edn. Academic, San Diego

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Praveena R, Sadasivam K, Deepha V, Sivakumar R (2014) Antioxidant potential of orientin: a combined experimental and DFT approach. J Mol Struct 1061:114–123

    Article  CAS  Google Scholar 

  • Rawdin BJ, Mellon SH, Dhabhar FS, Epel ES, Puterman E, Su Y et al (2013) Dysregulated relationship of inflammation and oxidative stress in major depression. Brain Behav Immun 31:143–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Réus GZ, Abelaira HM, dos Santos MA, Carlessi AS, Tomaz DB, Neotti MV, Liranço JL, Gubert C, Barth M, Kapczinski F, Quevedo J (2013) Ketamine and imipramine in the nucleus accumbens regulate histone deacetylation induced by maternal deprivation and are critical for associated behaviors. Behav Brain Res 256:451–456

    Article  PubMed  Google Scholar 

  • Réus GZ, Abelaira HM, Maciel AL, Dos Santos MA, Carlessi AS, Steckert AV et al (2015a) Minocycline protects against oxidative damage and alters energy metabolism parameters in the brain of rats subjected to chronic mild stress. Metab Brain Dis 30:545–553

    Article  PubMed  Google Scholar 

  • Réus GZ, Carlessi AS, Titus SE, Abelaira HM, Ignácio ZM, da Luz JR, Matias BI, Bruchchen L, Florentino D, Vieira A, Petronilho F, Quevedo J (2015b) A single dose of S-ketamine induces long-term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation. Dev Neurobiol [Epub ahead of print]

  • Rezin GT, Gonçalves CL, Daufenbach JF, Fraga DB, Santos PM, Ferreira GK et al (2009) Acute administration of ketamine reverses the inhibition of mitochondrial respiratory chain induced by chronic mild stress. Brain Res Bull 79:418–421

    Article  CAS  PubMed  Google Scholar 

  • Rice-Evans C (2001) Flavonoid antioxidants. Curr Med Chem 8:797–807

    Article  CAS  PubMed  Google Scholar 

  • Russo SJ, Nestler EJ (2013) The brain reward circuitry in mood disorders. Nat Rev Neurosci 14:609–625

    Article  CAS  PubMed  Google Scholar 

  • Rustin P, Chretien D, Bourgeron T, Gérard B, Rötig A, Saudubray JM et al (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228:35–51

    Article  CAS  PubMed  Google Scholar 

  • Sayre LM, Perry G, Smith MA (2008) Oxidative stress and neurotoxicity. Chem Res Toxicol 21:172–188

    Article  PubMed  Google Scholar 

  • Streck EL, Gonçalves CL, Furlanetto CB, Scaini G, Dal-Pizzol F, Quevedo J (2014) Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders. Rev Bras Psiquiatr 36:156–167

    Article  PubMed  Google Scholar 

  • Suzuki E, Nakaki T, Shintani F, Kanba S, Miyaoka H (2002a) Antipsychotic, antidepressant, anxiolytic, and anticonvulsant drugs induce type II nitric oxide synthase mRNA in rat brain. Neurosci Lett 333:217–219

    Article  CAS  PubMed  Google Scholar 

  • Suzuki E, Nakaki T, Kanba S, Inada K, Yokoyama M, Maruta H, Miyaoka H (2002b) Oral administration of imipramine increased nitrate in rat hypothalamus. Int J Neuropsychopharmacol 5:101–102

    Google Scholar 

  • Talhi O, Silva AMS (2012) Advances in C-glycosylflavonoid research. Curr Org Chem 16:859–896

    Article  CAS  Google Scholar 

  • Tomaz VS, Cordeiro RC, Costa AM, de Lucena DF, NobreJúnior HV, de Sousa FC et al (2014) Antidepressant-like effect of nitric oxide synthase inhibitors and sildenafil against lipopolysaccharide-induced depressive-like behavior in mice. Neuroscience 268:236–246

    Article  CAS  PubMed  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84

    Article  CAS  PubMed  Google Scholar 

  • Wagner H (2011) Synergy research: approaching a new generation of phytopharmaceuticals. Fitoterapia 82:34–47

    Article  PubMed  Google Scholar 

  • Xing G, Barry ES, Benford B, Grunberg NE, Li H, Watson WD et al (2013) Impact of repeated stress on traumatic brain injury-induced mitochondrial electron transport chain expression and behavioral responses in rats. Front Neurol 4:196

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan LJ, Lodge JK, Traber MG, Matsugo S, Packer L (1997) Comparison between copper-mediated and hypochlorite-mediated modifications of human low density lipoproteins evaluated by protein carbonyl formation. J Lipid Res 38:992–1001

    CAS  PubMed  Google Scholar 

  • Yap YW, Whiteman M, Cheung NS (2007) Chlorinative stress: an under appreciated mediator of neurodegeneration? Cell Signal 19:219–228

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Zhang GF, Wang N, Shi JY, Xu SX, Li XM, Ji MH et al (2013) Inhibition of the l-arginine-nitric oxide pathway mediates the antidepressant effects of ketamine in rats in the forced swimming test. Pharmacol Biochem Behav 110:8–12

    Article  CAS  PubMed  Google Scholar 

  • Zhou QG, Hu Y, Hua Y, Hu M, Luo CX, Han X et al (2007) Neuronal nitric oxide synthase contributes to chronic stress-induced depression by suppressing hippocampal neurogenesis. J Neurochem 103:1843–1854

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Laboratory of Neurosciences (Brazil) is a center within the National Institute for Translational Medicine (INCT-TM) and a member of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). This research was supported by grants from CNPq (JQ and GZR), FAPESC (JQ), Instituto Cérebro e Mente, and UNESC (JQ and ELS). JQ, FHR, and ELS are CNPq Research Fellows. C.F. ORTMANN is also grateful to CAPES for their research fellowship. Center for Translational Psychiatry (USA) is funded by Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston.

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Ortmann, C.F., Réus, G.Z., Ignácio, Z.M. et al. Enriched Flavonoid Fraction from Cecropia pachystachya Trécul Leaves Exerts Antidepressant-like Behavior and Protects Brain Against Oxidative Stress in Rats Subjected to Chronic Mild Stress. Neurotox Res 29, 469–483 (2016). https://doi.org/10.1007/s12640-016-9596-6

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