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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Effect of Bromelain on Chronic Unpredictable Stress-induced Behavioral, Biochemical, and Monoamine Changes in Wistar Albino Rat Model of Depression

Author(s): Rajeshwari Parasuraman, Dheepthi Jayamurali, Nivedita Manoharan and Sathya Narayanan Govindarajulu*

Volume 30, Issue 5, 2023

Published on: 10 May, 2023

Page: [411 - 426] Pages: 16

DOI: 10.2174/0929866530666230419093531

Price: $65

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Abstract

Background: Bromelain is a complex mixture of protease enzyme extract from the fruit or stem of the pineapple plant and it has a history of folk medicine use. It is known to have a wide range of biological actions and it is most commonly used as an anti-inflammatory agent, though scientists have also discovered its potential as an anticancer and antimicrobial agent, it has been reported to have positive effects on the respiratory, digestive, circulatory systems and potentially on the immune system.

Objective: This study was designed to investigate the antidepressant potential of Bromelain in the chronic unpredictable stress (CUS) model of depression.

Methods: We studied the antioxidant activity, and neuroprotective effect of Bromelain by analyzing the fear and anxiety behavior, antioxidants, and neurotransmitter levels, and also by analyzing the histopathological changes. Adult male Wistar albino rats were divided into 5 groups, Control; Bromelain; CUS; CUS + Bromelain, CUS + fluoxetine. Animals of the CUS group, CUS + Bromelain group, and CUS + Fluoxetine group were exposed to CUS for 30 days. Animals of the Bromelain group and CUS + Bromelain group were treated orally with 40 mg/kg Bromelain throughout the period of CUS whereas, the positive control group was treated with fluoxetine.

Results: Results showed a significant decrease in oxidative stress marker (lipid peroxidation), and the stress hormone cortisol, in Bromelain-treated CUS-induced depression. Bromelain treatment in CUS has also resulted in a significant increase in neurotransmitter levels, which indicates the efficacy of Bromelain to counteract the monamine neurotransmitter changes in depression by increasing their synthesis and reducing their metabolism. In addition, the antioxidant activity of Bromelain prevented oxidative stress in depressed rats. Also, hematoxylin and eosin staining of hippocampus sections has revealed that Bromelain treatment has protected the degeneration of nerve cells by chronic unpredictable stress exposure.

Conclusion: This data provides evidence for the antidepressant-like action of Bromelain by preventing neurobehavioral, biochemical, and monoamine alterations.

Keywords: Chronic unpredictable stress, depression, bromelain, fluoxetine, oxidative stress, monoamine neurotransmitters.

Graphical Abstract
[1]
Institute of Health Metrics and Evaluation. Global Health DataExchange (GHDx). Available from: http://ghdx.healthdata.org/gbd-results-tool?params=gbd-api-2019-permalink/d780dffbe8a381b25e1416884959e88b (Accessed on: 1 May 2021).
[2]
Moore, D.P.; Jefferson, J.W. Mood Disorders. In: Handbook of Medical Psychiatry, 2nd ed; Mosby Elsevier: Philadelphia, Pa, 2004, p. 74.
[3]
Trangle, M.; Gursky, J.; Haight, R.; Hardwig, J.; Hinnenkamp, T.; Kessler, D.; Mack, N.; Myszkowski, M. Institute for clinical systems improvement. Adult Depression in Primary Care, 2016, 12-15.
[4]
Evans-Lacko, S.; Aguilar-Gaxiola, S.; Al-Hamzawi, A.; Alonso, J.; Benjet, C.; Bruffaerts, R.; Chiu, W.T.; Florescu, S.; de Girolamo, G.; Gureje, O.; Haro, J.M.; He, Y.; Hu, C.; Karam, E.G.; Kawakami, N.; Lee, S.; Lund, C.; Kovess-Masfety, V.; Levinson, D.; Navarro-Mateu, F.; Pennell, B.E.; Sampson, N.A.; Scott, K.M.; Tachimori, H.; ten Have, M.; Viana, M.C.; Williams, D.R.; Wojtyniak, B.J.; Zarkov, Z.; Kessler, R.C.; Chatterji, S.; Thornicroft, G. Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: Results from the WHO World Mental Health (WMH) surveys. Psychol. Med., 2018, 48(9), 1560-1571.
[http://dx.doi.org/10.1017/S0033291717003336] [PMID: 29173244]
[5]
Bajpai, A.; Verma, A.K.; Srivastava, M.; Srivastava, R. Oxidative stress and major depression. J. Clin. Diagn. Res., 2014, 8(12), CC04-CC07.
[http://dx.doi.org/10.7860/JCDR/2014/10258.5292] [PMID: 25653939]
[6]
Maria Michel, T.; Pülschen, D.; Thome, J. The role of oxidative stress in depressive disorders. Curr. Pharm. Des., 2012, 18(36), 5890-5899.
[http://dx.doi.org/10.2174/138161212803523554] [PMID: 22681168]
[7]
Ravindran, A.V.; Balneaves, L.G.; Faulkner, G.; Ortiz, A.; McIntosh, D.; Morehouse, R.L.; Ravindran, L.; Yatham, L.N.; Kennedy, S.H.; Lam, R.W.; MacQueen, G.M.; Milev, R.V.; Parikh, S.V. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder. Can. J. Psychiatry, 2016, 61(9), 576-587.
[http://dx.doi.org/10.1177/0706743716660290] [PMID: 27486153]
[8]
Cipriani, A.; Furukawa, T.A.; Salanti, G.; Chaimani, A.; Atkinson, L.Z.; Ogawa, Y.; Leucht, S.; Ruhe, H.G.; Turner, E.H.; Higgins, J.P.T.; Egger, M.; Takeshima, N.; Hayasaka, Y.; Imai, H.; Shinohara, K.; Tajika, A.; Ioannidis, J.P.A.; Geddes, J.R. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet, 2018, 391(10128), 1357-1366.
[http://dx.doi.org/10.1016/S0140-6736(17)32802-7] [PMID: 29477251]
[9]
Malberg, J.E.; Eisch, A.J.; Nestler, E.J.; Duman, R.S. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci., 2000, 20(24), 9104-9110.
[http://dx.doi.org/10.1523/JNEUROSCI.20-24-09104.2000] [PMID: 11124987]
[10]
John Rush, A.; Jain, S. Clinical Implications of the STAR*D Trial. In: Antidepressants: From biogenic amines to new mechanisms of action; Macaluso, M.; Preskorn, S.H., Eds.; Springer International Publishing: Cham, 2019; pp. 51-99.
[11]
Rush, A.J.; Trivedi, M.H.; Wisniewski, S.R.; Nierenberg, A.A.; Stewart, J.W.; Warden, D.; Niederehe, G.; Thase, M.E.; Lavori, P.W.; Lebowitz, B.D.; McGrath, P.J.; Rosenbaum, J.F.; Sackeim, H.A.; Kupfer, D.J.; Luther, J.; Fava, M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. Am. J. Psychiatry, 2006, 163(11), 1905-1917.
[http://dx.doi.org/10.1176/ajp.2006.163.11.1905] [PMID: 17074942]
[12]
Stubbs, B.; Vancampfort, D.; Hallgren, M.; Firth, J.; Veronese, N.; Solmi, M.; Brand, S.; Cordes, J.; Malchow, B.; Gerber, M.; Schmitt, A.; Correll, C.U.; De Hert, M.; Gaughran, F.; Schneider, F.; Kinnafick, F.; Falkai, P.; Möller, H.J.; Kahl, K.G. EPA guidance on physical activity as a treatment for severe mental illness: a meta-review of the evidence and Position Statement from the European Psychiatric Association (EPA), supported by the International Organization of Physical Therapists in Mental Health (IOPTMH). Eur. Psychiatry, 2018, 54, 124-144.
[http://dx.doi.org/10.1016/j.eurpsy.2018.07.004] [PMID: 30257806]
[13]
Chakraborty, A.J.; Mitra, S.; Tallei, T.E.; Tareq, A.M.; Nainu, F.; Cicia, D.; Dhama, K.; Emran, T.B.; Simal-Gandara, J.; Capasso, R. Bromelain a potential bioactive compound: A comprehensive overview from a pharmacological perspective. Life, 2021, 11(4), 317.
[http://dx.doi.org/10.3390/life11040317] [PMID: 33917319]
[14]
Hale, L.; Greer, P.; Trinh, C.; Gottfried, M. Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease. Clin. Immunol., 2005, 116(2), 135-142.
[http://dx.doi.org/10.1016/j.clim.2005.04.011] [PMID: 15936249]
[15]
Engwerda, C.R.; Andrew, D.; Murphy, M.; Mynott, T.L. Bromelain activates murine macrophages and natural killer cells in vitro. Cell. Immunol., 2001, 210(1), 5-10.
[http://dx.doi.org/10.1006/cimm.2001.1793] [PMID: 11485347]
[16]
Engwerda, C.R.; Andrew, D.; Ladhams, A.; Mynott, T.L. Bromelain modulates T cell and B cell immune responses in vitro and in vivo. Cell. Immunol., 2001, 210(1), 66-75.
[http://dx.doi.org/10.1006/cimm.2001.1807] [PMID: 11485354]
[17]
Barth, H.; Guseo, A.; Klein, R. In vitro study on the immunological effect of bromelain and trypsin on mononuclear cells from humans. Eur. J. Med. Res., 2005, 10(8), 325-331.
[PMID: 16131473]
[18]
Onken, J.E.; Greer, P.K.; Calingaert, B.; Hale, L.P. Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clin. Immunol., 2008, 126(3), 345-352.
[http://dx.doi.org/10.1016/j.clim.2007.11.002] [PMID: 18160345]
[19]
Bhui, K.; Tyagi, S.; Srivastava, A.K.; Singh, M.; Roy, P.; Singh, R.; Shukla, Y. Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G2/M arrest to apoptosis. Mol. Carcinog., 2012, 51(3), 231-243.
[http://dx.doi.org/10.1002/mc.20769] [PMID: 21432909]
[20]
Brakebusch, M.; Wintergerst, U.; Petropoulou, T.; Notheis, G.; Husfeld, L.; Belohradsky, B.H.; Adam, D. Bromelain is an accelerator of phagocytosis, respiratory burst and Killing of Candida albicans by human granulocytes and monocytes. Eur. J. Med. Res., 2001, 6(5), 193-200.
[PMID: 11410400]
[21]
Sartini, S.; Permana, A.D.; Mitra, S.; Tareq, A.M.; Salim, E.; Ahmad, I.; Harapan, H.; Emran, T.B.; Nainu, F. Current state and promising opportunities on pharmaceutical approaches in the treatment of polymicrobial diseases. Pathogens, 2021, 10(2), 245.
[http://dx.doi.org/10.3390/pathogens10020245] [PMID: 33672615]
[22]
Massimiliano, R.; Pietro, R.; Paolo, S.; Sara, P.; Michele, F. Role of bromelain in the treatment of patients with Pityriasis lichenoides chronica. J. Dermatolog. Treat., 2007, 18(4), 219-222.
[http://dx.doi.org/10.1080/09546630701299147] [PMID: 17671882]
[23]
Ako, H.; Cheung, A.H.; Matsuura, P.K. Isolation of a fibrinolysis enzyme activator from commercial bromelain. Arch. Int. Pharmacodyn. Ther., 1981, 254(1), 157-167.
[PMID: 7199897]
[24]
Krieger, Y.; Rosenberg, L.; Lapid, O.; Glesinger, R.; Bogdanov-Berezovsky, A.; Silberstein, E.; Sagi, A.; Judkins, K. Escharotomy using an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model. J. Trauma, 2005, 58(6), 1259-1264.
[http://dx.doi.org/10.1097/01.TA.0000169867.08607.F1] [PMID: 15995479]
[25]
Rosenberg, L.; Lapid, O.; Bogdanov-Berezovsky, A.; Glesinger, R.; Krieger, Y.; Silberstein, E.; Sagi, A.; Judkins, K.; Singer, A.J. Safety and efficacy of a proteolytic enzyme for enzymatic burn débridement: A preliminary report. Burns, 2004, 30(8), 843-850.
[http://dx.doi.org/10.1016/j.burns.2004.04.010] [PMID: 15555800]
[26]
Rakesh, R.L.; Prasad, A.; Kumar, D.; Sankar, M.; Nasir, A.; Latchumikanthan, A.; Kushwaha, B. In vitro evaluation of anthelmintic efficacy of Bromelain against goat gastrointestinal nematodes. J. Vet. Parasitol., 2016, 30, 68-74.
[27]
Golezar, S. Ananas comosus effect on perineal pain and wound healing after episiotomy: A randomized double-blind placebo-controlled clinical trial. Iran. Red Crescent Med. J., 2016, 18(3), e21019.
[http://dx.doi.org/10.5812/ircmj.21019] [PMID: 27247780]
[28]
Majid, O.W.; Al-Mashhadani, B.A. Perioperative bromelain reduces pain and swelling and improves quality of life measures after mandibular third molar surgery: A randomized, double-blind, placebo-controlled clinical trial. J. Oral Maxillofac. Surg., 2014, 72(6), 1043-1048.
[http://dx.doi.org/10.1016/j.joms.2013.12.035] [PMID: 24589242]
[29]
Walker, A.F.; Bundy, R.; Hicks, S.M.; Middleton, R.W. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine, 2002, 9(8), 681-686.
[http://dx.doi.org/10.1078/094471102321621269] [PMID: 12587686]
[30]
Mallik, D.; Deb, L.; Gandhare, B.; Bhattacharjee, C. Evaluation of ananascomosus fruit for antiulcer potentials on experimental animals. J. Harmonized Res. Appl. Sci., 2019, 7(2), 89.
[http://dx.doi.org/10.30876/JOHR.7.2.2019.89-97]
[31]
Saptarini, N.M.; Rahayu, D.; Kartikawati, E. Immunomodulatory activity of crude bromelain of pineapple (Ananascomosus (L.) Merr.), Crown from Subang District, Indonesia. Res. J. Pharm. Technol., 2020, 13(11), 5177-5182.
[http://dx.doi.org/10.5958/0974-360X.2020.00905.1]
[32]
Kumakura, S.; Yamashita, M.; Tsurufuji, S. Effect of bromelain on kaolin-induced inflammation in rats. Eur. J. Pharmacol., 1988, 150(3), 295-301.
[http://dx.doi.org/10.1016/0014-2999(88)90010-6] [PMID: 3046953]
[33]
Brien, S.; Lewith, G.; Walker, A.; Hicks, S.M.; Middleton, D. Bromelain as a treatment for osteoarthritis: A review of clinical studies. Evid. Based Complement. Alternat. Med., 2004, 1(3), 251-257.
[http://dx.doi.org/10.1093/ecam/neh035] [PMID: 15841258]
[34]
Juhasz, B.; Thirunavukkarasu, M.; Pant, R.; Zhan, L.; Penumathsa, S.V.; Secor, E.R., Jr; Srivastava, S.; Raychaudhuri, U.; Menon, V.P.; Otani, H.; Thrall, R.S.; Maulik, N. Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(3), H1365-H1370.
[http://dx.doi.org/10.1152/ajpheart.01005.2007] [PMID: 18192224]
[35]
Dighe, N.S.; Pattan, S.R.; Merekar, A.N.; Laware, R.B.; Bhawar, S.B.; Nirmal, S.N.; Gaware, V.M.; Hole, M.B.; Musmade, D.S.; Bromelain, A. Wonder supplement: A review. Pharmacologyonline, 2010, 1, 11-18.
[36]
Secor, E.R., Jr; Shah, S.J.; Guernsey, L.A.; Schramm, C.M.; Thrall, R.S. Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma. Altern. Ther. Health Med., 2012, 18(5), 9-17.
[PMID: 22894886]
[37]
Gabrielli, A.; Avvedimento, E.V.; Krieg, T. Scleroderma. N. Engl. J. Med., 2009, 360(19), 1989-2003.
[http://dx.doi.org/10.1056/NEJMra0806188] [PMID: 19420368]
[38]
Giller, F.B. The effect of bromelain on levels of penicillin in the cerebrospinal fluid of rabbits. Am. J. Pharm. Sci. Support. Public Health, 1962, 134, 238-244.
[PMID: 13898619]
[39]
Lotz-Winter, H. On the pharmacology of bromelain: An update with special regard to animal studies on dose-dependent effects. Planta Med., 1990, 56(3), 249-253.
[http://dx.doi.org/10.1055/s-2006-960949] [PMID: 2203073]
[40]
Mukherjee, D.; Bhattacharjee, P.; Bhattacharya, R.; Dutta, A.K.; Bhattacharyya, D. Degraded products of stem Bromelain destabilize aggregates of β-amyloid peptides involved in Alzheimer’s disease. Curr. Sci., 2018, 115(11), 2133-2141.
[http://dx.doi.org/10.18520/cs/v115/i11/2133-2141]
[41]
Gaspani, L.; Limiroli, E.; Ferrario, P.; Bianchi, M. In vivo and in vitro effects of bromelain on PGE(2) and SP concentrations in the inflammatory exudate in rats. Pharmacology, 2002, 65(2), 83-86.
[http://dx.doi.org/10.1159/000056191] [PMID: 11937778]
[42]
Rafiei-Asl, S.; Khadjeh, G.; Jalali, S.M.; Jamshidian, J.; Rezaie, A. Investigating the protective effects of Bromelain against inflammatory marker alterations induced by cadmium pulmonary intoxication in rat. Ir. Vet. J., 2020, 16(2), 75-88.
[http://dx.doi.org/10.22055/ivj.2019.192966.2163]
[43]
Jayakumar, S.; Raghunath, G.; Ilango, S.; Vijayakumar, J.; Vijayaraghavan, R. Effect of fluoxetine on the hippocampus of wistar albino rats in cold restraint stress model. J. Clin. Diagn. Res., 2017, 11(6), 1-6.
[http://dx.doi.org/10.7860/JCDR/2017/26958.9953]
[44]
Abdel Salam, O.M.E.; Mohammed, N.A.; Sleem, A.A.; Farrag, A.R. The effect of antidepressant drugs on thioacetamide-induced oxidative stress. Eur. Rev. Med. Pharmacol. Sci., 2013, 17(6), 735-744.
[PMID: 23609356]
[45]
Pandey, D.K.; Pati, D.; Joshi, A.; Mahesh, R. Chronic unpredictable stress: Possible animal model of comorbid depression. Int. J. Preclin. Pharm. Res., 2010, 1(1), 54-63.
[46]
Liu, L.; Zhou, X.; Zhang, Y.; Pu, J.; Yang, L.; Yuan, S.; Zhao, L.; Zhou, C.; Zhang, H.; Xie, P. Hippocampal metabolic differences implicate distinctions between physical and psychological stress in four rat models of depression. Transl. Psychiatry, 2018, 8(1), 4.
[http://dx.doi.org/10.1038/s41398-017-0018-1] [PMID: 29317595]
[47]
Liu, M.Y.; Yin, C.Y.; Zhu, L.J.; Zhu, X.H.; Xu, C.; Luo, C.X.; Chen, H.; Zhu, D.Y.; Zhou, Q.G. Sucrose preference test for measurement of stress-induced anhedonia in mice. Nat. Protoc., 2018, 13(7), 1686-1698.
[http://dx.doi.org/10.1038/s41596-018-0011-z] [PMID: 29988104]
[48]
Hazim, A.I.; Ramanathan, S.; Parthasarathy, S.; Muzaimi, M.; Mansor, S.M. Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats. J. Physiol. Sci., 2014, 64(3), 161-169.
[http://dx.doi.org/10.1007/s12576-014-0304-0] [PMID: 24464759]
[49]
Okajima, D.; Kudo, G.; Yokota, H. Antidepressant-like behavior in brain-specific angiogenesis inhibitor 2-deficient mice. J. Physiol. Sci., 2011, 61(1), 47-54.
[http://dx.doi.org/10.1007/s12576-010-0120-0] [PMID: 21110148]
[50]
Ashok, I. wankhar, D.; wankhar, W.; Sheeladevi, R. Neurobehavioral changes and activation of neurodegenerative apoptosis on long-term consumption of aspartame in the rat brain. J. Nutr. Intermed. Metab., 2015, 2(3-4), 76-85.
[http://dx.doi.org/10.1016/j.jnim.2015.09.001]
[51]
Belovicova, K.; Bogi, E.; Csatlosova, K.; Dubovicky, M. Animal tests for anxiety-like and depression-like behavior in rats. Interdiscip. Toxicol., 2017, 10(1), 40-43.
[http://dx.doi.org/10.1515/intox-2017-0006] [PMID: 30123035]
[52]
Singh, D.K.; Verma, R. Spectrophotometric determination of corticosteroids and its application in pharmaceutical formulation. Iran. J. Pharmacol. Ther., 2008, 7, 61-65.
[53]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, 95(2), 351-358.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[54]
Marklund, S.; Marklund, G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem., 1974, 47(3), 469-474.
[http://dx.doi.org/10.1111/j.1432-1033.1974.tb03714.x] [PMID: 4215654]
[55]
Rotruck, J.T.; Pope, A.L.; Ganther, H.E.; Swanson, A.B.; Hafeman, D.G.; Hoekstra, W.G. Selenium: Biochemical role as a component of glutathione peroxidase. Science, 1973, 179(4073), 588-590.
[http://dx.doi.org/10.1126/science.179.4073.588] [PMID: 4686466]
[56]
Moron, M.; Depierre, J.; Mannervik, B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim. Biophys. Acta, Gen. Subj., 1979, 582(1), 67-78.
[http://dx.doi.org/10.1016/0304-4165(79)90289-7] [PMID: 760819]
[57]
Omaye, S.T.; David Turnbull, J.; Sauberlich, H.E. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol., 1979, 62, 3-11.
[http://dx.doi.org/10.1016/0076-6879(79)62181-X] [PMID: 440112]
[58]
Rahman, H.; Eswaraiah, M.C. Simple spectroscopic methods for estimating. brain neurotransmitters, antioxidant enzymes of laboratory animals like mice: A review; Pharmatutor, 2012.
[59]
Boyina, R.; Dodoala, S. Evaluation of the neurobehavioural toxic effects of taurine, glucuronolactone, and gluconolactone used in energy drinks in young rats. Turk J Pharm Sci, 2020, 17(6), 659-666.
[http://dx.doi.org/10.4274/tjps.galenos.2019.33602] [PMID: 33389968]
[60]
Morton, J.F. Fruits of warm climates. Pineapple., 1987, 517, 18-28.
[61]
Saptarini, N.; Rahayu, D.; Herawati, I. Antioxidant activity of crude bromelain of pineapple (Ananas comosus (L.) Merr) crown from Subang district, Indonesia. J. Pharm. Bioallied Sci., 2019, 11(8), 551.
[http://dx.doi.org/10.4103/jpbs.JPBS_200_19] [PMID: 32148362]
[62]
Rathnavelu, V.; Alitheen, N.B.; Sohila, S.; Kanagesan, S.; Ramesh, R. Potential role of bromelain in clinical and therapeutic applications. Biomed. Rep., 2016, 5(3), 283-288.
[http://dx.doi.org/10.3892/br.2016.720] [PMID: 27602208]
[63]
Lee, J-H.; Lee, J-B.; Lee, J-T.; Park, H-R.; Kim, J-B. Medicinal effects of bromelain (Ananas comosus) targeting oral environment as an anti-oxidant and anti-inflammatory agent. J. Food Nutr. Res., 2018, 6(12), 773-784.
[http://dx.doi.org/10.12691/jfnr-6-12-8]
[64]
Uttara, B.; Singh, A.; Zamboni, P.; Mahajan, R. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[65]
Singh, A.; Kukreti, R.; Saso, L.; Kukreti, S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules, 2019, 24(8), 1583.
[http://dx.doi.org/10.3390/molecules24081583] [PMID: 31013638]
[66]
Chaudhary, B.; Agarwal, S.; Bist, R. Invulnerability of bromelain against oxidative degeneration and cholinergic deficits imposed by dichlorvos in mice brains. Front. Biol., 2018, 13(1), 56-62.
[http://dx.doi.org/10.1007/s11515-018-1479-1]
[67]
Blossom, V.; Gokul, M.; Kumar, N.A.; Kini, R.D.; Nayak, S.; Bhagyalakshmi, K. Chronic unpredictable stress-induced inflammation and quantitative analysis of neurons of distinct brain regions in Wistar rat model of comorbid depression. Vet. World, 2020, 13(9), 1870-1874.
[http://dx.doi.org/10.14202/vetworld.2020.1870-1874] [PMID: 33132599]
[68]
Lupien, S.J.; McEwen, B.S.; Gunnar, M.R.; Heim, C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci., 2009, 10(6), 434-445.
[http://dx.doi.org/10.1038/nrn2639] [PMID: 19401723]
[69]
Sousa, N.; Almeida, O.F.X. Disconnection and reconnection: the morphological basis of (mal)adaptation to stress. Trends Neurosci., 2012, 35(12), 742-751.
[http://dx.doi.org/10.1016/j.tins.2012.08.006] [PMID: 23000140]
[70]
Oliveira, T.G.; Chan, R.B.; Bravo, F.V.; Miranda, A.; Silva, R.R.; Zhou, B.; Marques, F.; Pinto, V.; Cerqueira, J.J.; Di Paolo, G.; Sousa, N. The impact of chronic stress on the rat brain lipidome. Mol. Psychiatry, 2016, 21(1), 80-88.
[http://dx.doi.org/10.1038/mp.2015.14] [PMID: 25754084]
[71]
Kurosinski, P.; Götz, J. Glial cells under physiologic and pathologic conditions. Arch. Neurol., 2002, 59(10), 1524-1528.
[http://dx.doi.org/10.1001/archneur.59.10.1524] [PMID: 12374489]
[72]
Halliwell, B. Reactive oxygen species and the central nervous system. J. Neurochem., 1992, 59(5), 1609-1623.
[http://dx.doi.org/10.1111/j.1471-4159.1992.tb10990.x] [PMID: 1402908]
[73]
Wang, X.; Michaelis, M.L.; Michaelis, E.K. Functional genomics of brain aging and Alzheimer’s disease: Focus on selective neuronal vulnerability. Curr. Genomics, 2010, 11(8), 618-633.
[http://dx.doi.org/10.2174/138920210793360943] [PMID: 21629439]
[74]
Pothion, S.; Bizot, J.C.; Trovero, F.; Belzung, C. Strain differences in sucrose preference and in the consequences of unpredictable chronic mild stress. Behav. Brain Res., 2004, 155(1), 135-146.
[http://dx.doi.org/10.1016/j.bbr.2004.04.008] [PMID: 15325787]
[75]
Leite, J.A.; Orellana, A.M.M.; Kinoshita, P.F.; de Mello, N.P.; Scavone, C.; Kawamoto, E.M. Neuroinflammation and Neurotransmission Mechanisms Involved in Neuropsychiatric Disorders. In: Mechanisms of Neuroinflammation; Intechopen, 2017.
[http://dx.doi.org/10.5772/intechopen.69343]
[76]
Briley, M.; Chantal, M. The importance of norepinephrine in depression. Neuropsychiatr. Dis. Treat., 2011, 7(1), 9-13.
[http://dx.doi.org/10.2147/NDT.S19619] [PMID: 21750623]
[77]
Gilabert-Juan, J.; Castillo-Gomez, E.; Guirado, R.; Moltó, M.D.; Nacher, J. Chronic stress alters inhibitory networks in the medial prefrontal cortex of adult mice. Brain Struct. Funct., 2013, 218(6), 1591-1605.
[http://dx.doi.org/10.1007/s00429-012-0479-1] [PMID: 23179864]
[78]
Du, X.; Yin, M.; Yuan, L.; Zhang, G.; Fan, Y.; Li, Z.; Yuan, N.; Lv, X.; Zhao, X.; Zou, S.; Deng, W.; Kosten, T.R.; Zhang, X.Y. Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus. Transl. Psychiatry, 2020, 10(1), 130.
[http://dx.doi.org/10.1038/s41398-020-0808-8] [PMID: 32366842]
[79]
Fuchs, E.; Czéh, B.; Kole, M.H.P.; Michaelis, T.; Lucassen, P.J. Alterations of neuroplasticity in depression: The hippocampus and beyond. Eur. Neuropsychopharmacol., 2004, 14(5), S481-S490.
[http://dx.doi.org/10.1016/j.euroneuro.2004.09.002] [PMID: 15550346]
[80]
Bremner, J.D.; Narayan, M.; Anderson, E.R.; Staib, L.H.; Miller, H.L.; Charney, D.S. Hippocampal volume reduction in major depression. Am. J. Psychiatry, 2000, 157(1), 115-118.
[http://dx.doi.org/10.1176/ajp.157.1.115] [PMID: 10618023]

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