Abstract
The present study evaluates the potential of neuroprotective phytochemicals-rutin (R), resveratrol (Res), 17β-estradiol (17β-E2), and their different combinations against chronic immobilization stress (CIS)-induced depression-like behaviour in male albino mice. Here, the mice were exposed to stress via immobilization of their four limbs under a restrainer for 6 h daily until 7 days of the induction after 30 min of respective drug treatment in different mice groups. The result found the protective effect of these phytoconstituents and their combinations against CIS-induced depression due to their ability to suppress oxidative stress, restore mitochondria, HPA-axis modulation, neurotransmitter level, stress hormones, and inflammatory markers. Also, the combination drug regimens of these phytoconstituents showed synergistic results in managing the physiological and biochemical features of depression. Thus, these neuroprotective could be utilized well in combination to manage depression-like symptoms during episodic stress. Furthermore, such results could be well justified when administered in polyherbal formulation with these neuroprotective as major components. In addition, an advanced study can be designed at the molecular and epigenetics level using a formulation based on these neuroprotective.
Similar content being viewed by others
Data Availability Statement
Data will be provided by the corresponding author upon request.
References
Aggarwal A, Gaur V, Kumar A (2010) Nitric oxide mechanism in the protective effect of naringin against post-stroke depression (PSD) in mice Life Sci 86(25-26):928–935. https://doi.org/10.1016/j.lfs.2010.04.011
Aherne SA, O’Brien NM (2000) Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide-and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radical Biol Med 29(6):507–514. https://doi.org/10.1016/S0891-5849(00)00360-9
Andreazza AC, Kauer-Sant’Anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, Yatham LN (2008) Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord 111(2–3):135–144. https://doi.org/10.1016/j.jad.2008.04.013
Ates O, Cayli S, Altinoz E, Gurses I, Yucel N, Kocak A et al (2006) Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury. Acta Pharmacol Sin 27(10):1317–1325. https://doi.org/10.1111/j.1745-7254.2006.00416.x
Alesci S, Martinez PE, Kelkar S, Ilias I, Ronsaville DS, Listwak SJ, Ayala AR, Licinio J, Gold HK, Kling MA, Chrousos GP, Gold PW (2005) Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications. J Clin Endocrinol Metab 90(5):2522–30. https://doi.org/10.1210/jc.2004-1667
Baik JH (2020) Stress and the dopaminergic reward system. Exp Mol Med 52(12):1879–1890. https://doi.org/10.1038/s12276-020-00532-4
Barden N (2004) Implication of the hypothalamic–pituitary–adrenal axis in the physiopathology of depression. J Psychiatry Neurosci 29(3):185
Bazhan N, Zelena D (2013) Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis. Brain Res Bull 95:46–53. https://doi.org/10.1016/j.brainresbull.2013.04.002
Bhutani MK, Bishnoi M, Kulkarni SK (2009) Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol Biochem Behav 92(1):39–43. https://doi.org/10.1016/j.pbb.2008.10.007
Capra JC, Cunha MP, Machado DG, Zomkowski AD, Mendes BG, Santos ARS et 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(2–3):232–238. https://doi.org/10.1016/j.ejphar.2010.06.043
Cecchi M, Khoshbouei H, Morilak DA (2002) Modulatory effects of norepinephrine, acting on alpha1 receptors in the central nucleus of the amygdala, on behavioral and neuroendocrine responses to acute immobilization stress. Neuropharmacology 43(7):1139–1147. https://doi.org/10.1016/S0028-3908(02)00292-7
Cengiz T, Kara SH, Caliyurt O, Vardar E, Abay E (2003) Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology 170(4):429–433. https://doi.org/10.1007/s00213-003-1566-z
Chen WJ, Du JK, Hu X, Yu Q, Li DX, Wang CN et al (2017) Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior. Physiol Behav 182:54–61. https://doi.org/10.1016/j.physbeh.2017.09.024
Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, Kunugi H (2012) Chronic restraint stress causes anxiety-and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 39(1):112–119. https://doi.org/10.1016/j.pnpbp.2012.05.018
Dallman MF, Pecoraro NC, la Fleur SE (2005) Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Behav Immun 19(4):275–280. https://doi.org/10.1016/j.bbi.2004.11.004
Dimpfel W (2009) Rat electropharmacograms of the flavonoids rutin and quercetin in comparison to those of moclobemide and clinically used reference drugs suggest antidepressive and/or neuroprotective action. Phytomedicine 16(4):287–294. https://doi.org/10.1016/j.phymed.2009.02.005
Dhir A, Padi SS, Naidu PS, Kulkarni SK (2006) Protective effect of naproxen (non-selective COX-inhibitor) or rofecoxib (selective COX-2 inhibitor) on immobilization stress-induced behavioral and biochemical alterations in mice. Eur J Pharmacol 535(1-3):192–198. https://doi.org/10.1016/j.ejphar.2006.01.064
Einat H, Yuan P, Manji HK (2005) Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disorders. Behav Brain Res 165(2):172–180. https://doi.org/10.1016/j.bbr.2005.06.012
Fava M, Kendler KS (2000) Major depressive disorder. Neuron 28(2):335–341
Felger JC, Lotrich FE (2013) Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 246:199–229. https://doi.org/10.1016/j.neuroscience.2013.04.060
Franco JL, Braga HC, Stringari J, Missau FC, Posser T, Mendes BG, Leal RB, Santos AR, Dafre AL, Pizzolatti MG (2007) Mercurial-induced hydrogen peroxide generation in mouse brain mitochondria: protective effects of quercetin. Chem Res Toxicol 20(12):1919–1926. https://doi.org/10.1021/tx7002323
Frémont L (2000) Biological effects of resveratrol. Life Sci 66(8):663–673. https://doi.org/10.1016/S0024-3205(99)00410-5
Fukui K, Onodera K, Shinkai T, Suzuki S, Urano S (2001) Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems. Ann N Y Acad Sci 928:168–75. https://doi.org/10.1111/j.1749-6632.2001.tb05646.x
Garcia-Segura LM, Azcoitia I, DonCarlos LL (2001) Neuroprotection by estradiol. Prog Neurobiol 63(1):29–60. https://doi.org/10.1016/S0301-0082(00)00025-3
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 114:64–69. https://doi.org/10.1016/S0301-0082(00)00025-3
Green PS, Simpkins JW (2000) Neuroprotective effects of estrogens: potential mechanisms of action. Int J Dev Neurosci 18(4–5):347–358. https://doi.org/10.1016/S0736-5748(00)00017-4
Gregus A, Wintink AJ, Davis AC, Kalynchuk LE (2005) Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats. Behav Brain Res 156(1):105–114. https://doi.org/10.1016/j.bbr.2004.05.013
Heiderstadt K, McLaughlin R, Wrighe D, Walker S, Gomez-Sanchez C (2000) The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats. Lab Anim 34(1):20–28. https://doi.org/10.1258/002367700780578028
Holsboer F (2001) Stress, hypercortisolism and corticosteroid receptors in depression: implicatons for therapy. J Affect Disord 62(1–2):77–91. https://doi.org/10.1016/S0165-0327(00)00352-9
Horchar MJ, Wohleb ES (2019) Glucocorticoid receptor antagonism prevents microglia-mediated neuronal remodeling and behavioral despair following chronic unpredictable stress. Brain Behav Immun 81:329–340. https://doi.org/10.1016/j.bbi.2019.06.030
Hu Y, Cardounel A, Gursoy E, Anderson P, Kalimi M (2000) Anti-stress effects of dehydroepiandrosterone: protection of rats against repeated immobilization stress-induced weight loss, glucocorticoid receptor production, and lipid peroxidation. Biochem Pharmacol 59(7):753–762. https://doi.org/10.1016/s0006-2952(99)00385-8
Huang HJ, Zhu XC, Han QQ, Wang YL, Yue N, Wang J et al (2017) Ghrelin alleviates anxiety-and depression-like behaviors induced by chronic unpredictable mild stress in rodents. Behav Brain Res 326:33–43. https://doi.org/10.1016/j.bbr.2017.02.040
Huang D, Zhang L, Yang JQ, Luo Y, Cui T, Du TT, Jiang XH (2019) Evaluation on monoamine neurotransmitters changes in depression rats given with sertraline, meloxicam or/and caffeic acid. Genes Dis 6(2):167–175. https://doi.org/10.1016/j.gendis.2018.05.005
Joseph DN, Whirledge S (2017) Stress and the HPA axis: balancing homeostasis and fertility. Int J Mol Sci 18(10):2224. https://doi.org/10.3390/ijms18102224
Kasala ER, Bodduluru LN, Maneti Y, Thipparaboina R (2014) Effect of meditation on neurophysiological changes in stress mediated depression. Complement Ther Clin Pract 20(1):74-80. https://doi.org/10.1016/j.ctcp.2013.10.001
Konstandi M, Johnson E, Lang MA, Malamas M, Marselos M (2000) Noradrenaline, dopamine, serotonin: different effects of psychological stress on brain biogenic amines in mice and rats. Pharmacol Res 41(3):341–346. https://doi.org/10.1006/phrs.1999.0597
Kulkarni SK, Dhir A (2008) Withania somnifera: an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry 32(5):1093–1105. https://doi.org/10.1016/j.pnpbp.2007.09.011
Kulkarni SK, Bhutani MK, Bishnoi M (2008) Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 201(3):435–442. https://doi.org/10.1007/s00213-008-1300-y
Kumar A, Garg R (2009) Protective effects of antidepressants against chronic fatigue syndrome–induced behavioral changes and biochemical alterations. Fundam Clin Pharmacol 23(1):89–95. https://doi.org/10.1111/j.1472-8206.2008.00638.x
Kumar A, Goyal R (2008) Quercetin protects against acute immobilization stress-induced behaviors and biochemical alterations in mice. J Med Food 11(3):469–473. https://doi.org/10.1089/jmf.2006.0207
Kumar A, Garg R, Kumar P (2008) Nitric oxide modulation mediates the protective effect of trazodone in a mouse model of chronic fatigue syndrome. Pharmacol Rep 60(5):664
Kumar A, Goyal R, Prakash A (2009) Possible GABAergic mechanism in the protective effect of allopregnenolone against immobilization stress. Eur J Pharmacol 602(2–3):343–347. https://doi.org/10.1016/j.ejphar.2008.11.038
Kumar A, Garg R, Gaur V, Kumar P (2010) Venlafaxine involves nitric oxide modulatory mechanism in experimental model of chronic behavior despair in mice. Brain Res 1311:73–80. https://doi.org/10.1016/j.brainres.2009.11.050
Kumari B, Kumar A, Dhir A (2007) Protective effect of non-selective and selective COX-2-inhibitors in acute immobilization stress-induced behavioral and biochemical alterations. Pharmacol Rep 59(6):699–707
Lee HC, Chang DE, Yeom M, Kim GH, Choi KD, Shim I et al (2005) Gene expression profiling in hypothalamus of immobilization-stressed mouse using cDNA microarray. Mol Brain Res 135(1–2):293–300. https://doi.org/10.1016/j.molbrainres.2004.11.016
Levkovitz Y, Gil-Ad I, Zeldich E, Dayag M, Weizman A (2005) Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines. J Mol Neurosci 27(1):29–42. https://doi.org/10.1385/JMN:27:1:029
Li Y, Couch L, Higuchi M, Fang JL, Guo L (2012) Mitochondrial dysfunction induced by sertraline, an antidepressant agent. Toxicol Sci 127(2):582–591. https://doi.org/10.1093/toxsci/kfs100
Luca M, Luca A, Calandra C (2013) Accelerated aging in major depression: the role of nitro-oxidative stress. Oxid Med Cell Longev. https://doi.org/10.1155/2013/230797
Ma S, Morilak DA (2005) Norepinephrine release in medial amygdala facilitates activation of the hypothalamic-pituitary-adrenal axis in response to acute immobilisation stress. J Neuroendocrinol 17(1):22–28. https://doi.org/10.1111/j.1365-2826.2005.01279.x
Machado DG, Bettio LE, Cunha MP, Santos AR, Pizzolatti MG, Brighente IM, Rodrigues ALS (2008) Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems. Eur J Pharmacol 587(1–3):163–168. https://doi.org/10.1016/j.ejphar.2008.03.021
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(3):676–692. https://doi.org/10.1016/j.pnpbp.2010.05.004
Manoli I, Alesci S, Blackman MR, Su YA, Rennert OM, Chrousos GP (2007) Mitochondria as key components of the stress response. Trends Endocrinol Metab 18(5):190–198. https://doi.org/10.1016/j.tem.2007.04.004
Marais L, Van Rensburg SJ, Van Zyl JM, Stein DJ, Daniels WM (2008) Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus. Neurosci Res 61(1):106–112. https://doi.org/10.1016/j.neures.2008.01.011
Martínez-Martos JM, Ramírez-Expósito MJ, Mayas-Torres MD, García-López MJ, Ramírez-Sánchez M (2000) Utility of the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to measure mitochondrial activity in K+ and ATP-stimulated rodent cortex synaptosomes. Neurosci Res Commun 27(2):103–107. https://doi.org/10.1002/1520-6769(200009/10)27:2%3C103
Mayevsky A (2009) Mitochondrial function and energy metabolism in cancer cells: past overview and future perspectives. Mitochondrion 9(3):165–179. https://doi.org/10.1016/j.mito.2009.01.009
Michel TM, Frangou S, Thiemeyer D, Camara S, Jecel J, Nara K et al (2007) Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder—a postmortem study. Psychiatry Res 151(1–2):145–150. https://doi.org/10.1016/j.psychres.2006.04.013
Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M (2001) Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol 11(3):203–208. https://doi.org/10.1016/S0924-977X(01)00081-5
Mineur YS, Belzung C, Crusio WE (2006) Effects of unpredictable chronic mild stress on anxiety and depression-like behavior in mice. Behav Brain Res 175(1):43–50. https://doi.org/10.1016/j.bbr.2006.07.029
Mikstacka R, Rimando AM, Ignatowicz E (2010) Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant Foods Hum Nutr 65(1):57–63. https://doi.org/10.1007/s11130-010-0154-8
Molina-Hernández M, Téllez-Alcántara NP, Olivera-Lopez JI, Jaramillo MT (2009) Olanzapine plus 17-β estradiol produce antidepressant-like actions in rats forced to swim. Pharmacol Biochem Behav 93(4):491–497. https://doi.org/10.1016/j.pbb.2009.06.015
Mundugaru R, Sivanesan S, Udaykumar P, Vidyadhara DJ, Prabhu SN, Ravishankar B (2018) Neuroprotective functions of Alpinia galanga in forebrain ischemia induced neuronal damage and oxidative insults in rat hippocampus. Indian J Pharm Educ Res 52:s77–s85. https://doi.org/10.5530/ijper.52.4s.79
Munhoz CD, Garcia-Bueno B, Madrigal JLM, Lepsch LB, Scavone C, Leza JC (2008) Stress-induced neuroinflammation: mechanisms and new pharmacological targets. Braz J Med Biol Res 41:1037–1046. https://doi.org/10.1590/s0100-879x2008001200001
Musselman DL, Miller AH, Porter MR, Manatunga A, Gao F, Penna S et al (2001) Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry 158(8):1252–1257. https://doi.org/10.1176/appi.ajp.158.8.1252
Nakayama M, Aihara M, Chen YN, Araie M, Tomita-Yokotani K, Iwashina T (2011) Neuroprotective effects of flavonoids on hypoxia-, glutamate-, and oxidative stress–induced retinal ganglion cell death. Mol vis 17:1784
Navarro KL, Huss M, Smith JC, Sharp P, Marx JO, Pacharinsak C (2021) Mouse Anesthesia: the art and science. ILAR J/nat Res Council Inst Lab Anim Resour. https://doi.org/10.1093/ilar/ilab016
Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiat 59(12):1151–1159. https://doi.org/10.1016/j.biopsych.2005.09.018
Österlund MK (2010) Underlying mechanisms mediating the antidepressant effects of estrogens. Biochimica Et Biophysica Acta (BBA)-General Subjects 1800(10):1136–1144. https://doi.org/10.1016/j.bbagen.2009.11.001
Pachauri SD, Tota S, Khandelwal K, Verma PRP, Nath C, Hanif K et al (2012) Protective effect of fruits of Morinda citrifolia L. on scopolamine induced memory impairment in mice: a behavioral, biochemical and cerebral blood flow study. J Ethnopharmacol 139(1):34–41. https://doi.org/10.1016/j.jep.2011.09.057
Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31(9):464–468. https://doi.org/10.1016/j.tins.2008.06.006
Picard M, McEwen BS (2018) Psychological stress and mitochondria: a conceptual framework. Psychosomatic Med 80(2):126. https://doi.org/10.1097/PSY.0000000000000544
Tasset I, Peña J, Jimena I, Feijóo M, Del Carmen Muñoz M, Montilla P, Túnez I (2008) Effect of 17beta-estradiol on olfactory bulbectomy-induced oxidative stress and behavioral changes in rats. Neuropsychiatr Dis Treat 4(2):441–449
Tuglu C, Kara SH, Caliyurt O, Vardar E, Abay E (2003) Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology (Berl) 170(4):429–33. https://doi.org/10.1007/s00213-003-1566-z
Quincozes-Santos A, Nardin P, De Souza DF, Gelain DP, Moreira JC, Latini A et al (2009) The janus face of resveratrol in astroglial cells. Neurotox Res 16(1):30–41. https://doi.org/10.1007/s12640-009-9042-0
Quiroz JA, Gray NA, Kato T, Manji HK (2008) Mitochondrially mediated plasticity in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology 33(11):2551–2565. https://doi.org/10.1038/sj.npp.1301671
Raison CL, Capuron L, Miller AH (2006) Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 27(1):24–31. https://doi.org/10.1016/j.it.2005.11.006
Ramkumar K, Srikumar BN, Rao S, Raju TR (2008) Self-stimulation rewarding experience restores stress-induced CA3 dendritic atrophy, spatial memory deficits and alterations in the levels of neurotransmitters in the hippocampus. Neurochem Res 33(9):1651–1662. https://doi.org/10.1007/s11064-007-9511-x
Rather SA, Sarumathi A, Anbu S, Saravanan N (2013) Gallic acid protects against immobilization stress-induced changes in wistar rats. J Stress Physiol Biochem 9(1):136–147
Rezin GT, Cardoso MR, Gonçalves CL, Scaini G, Fraga DB, Riegel RE et al (2008) Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int 53(6–8):395–400. https://doi.org/10.1016/j.neuint.2008.09.012
Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL (2009) Mitochondrial dysfunction and psychiatric disorders. Neurochem Res 34(6):1021–1029. https://doi.org/10.1007/s11064-008-9865-8
Goyal R, Kumar A (2007) Protective effect of alprazolam in acute immobilization stress-induced certain behavioral and biochemical alterations in mice. Pharmacol Rep 59(3):284–90
Scaini G, Maggi DD, De-Nês BT, Gonçalves CL, Ferreira GK, Teodorak BP et al (2011) Activity of mitochondrial respiratory chain is increased by chronic administration of antidepressants. Acta Neuropsychiatrica 23(3):112–118
Seppet E, Gruno M, Peetsalu A, Gizatullina Z, Nguyen HP, Vielhaber S et al (2009) Mitochondria and energetic depression in cell pathophysiology. Int J Mol Sci 10(5):2252–2303. https://doi.org/10.3390/ijms10052252
Shang J, Yan H, Jiao Y, Ohta Y, Liu X, Li X et al (2018) Therapeutic effects of pretreatment with tocovid on oxidative stress in postischemic mice brain. J Stroke Cerebrovasc Dis 27(8):2096–2105. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.03.012
Szuster-Ciesielska A, Słotwińska M, Stachura A, Marmurowska-Michałowska H, Dubas-Ślemp H, Bojarska-Junak A, Kandefer-Szerszeń M (2008) Accelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 32(3):686–694. https://doi.org/10.1016/j.pnpbp.2007.11.012
Torres SJ, Nowson CA (2007) Relationship between stress, eating behavior, and obesity. Nutrition 23(11–12):887–894. https://doi.org/10.1016/j.nut.2007.08.008
Ungvari Z, Sonntag WE, de Cabo R, Baur JA, Csiszar A (2011) Mitochondrial protection by resveratrol. Exercise Sport Sci Rev 39(3):128. https://doi.org/10.1097/JES.0b013e3182141f80
Wang Q, Fan W, Cai Y, Wu Q, Mo L, Huang Z, Huang H (2016) Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow. Amino Acids 48(9):2169–2177. https://doi.org/10.1007/s00726-016-2244-x
Wang P, Li B, Fan J, Zhang K, Yang W, Ren B, Cui R (2019) Additive antidepressant-like effects of fasting with β-estradiol in mice. J Cell Mol Med 23(8):5508–5517. https://doi.org/10.1111/jcmm.14434
Xu Y, Wang Z, You W, Zhang X, Li S, Barish PA et al (2010) Antidepressant-like effect of trans-resveratrol: involvement of serotonin and noradrenaline system. Eur Neuropsychopharmacol 20(6):405–413. https://doi.org/10.1016/j.euroneuro.2010.02.013
Yan HC, Cao X, Das M, Zhu XH, Gao TM (2010) Behavioral animal models of depression. Neurosci Bull 26(4):327–337. https://doi.org/10.1007/s12264-010-0323-7
Yune TY, Kim SJ, Lee SM, Lee YK, Oh YJ, Kim YC et al (2004) Systemic administration of 17β-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma 21(3):293–306. https://doi.org/10.1089/089771504322972086
Funding
This study was not supported by any funding agencies.
Author information
Authors and Affiliations
Contributions
IAI carried out the bench work; MA contributed equally with IAI in carrying out the wet laboratory work; SGA analysed the results and applied statistics; VK supervised the study.
Corresponding author
Ethics declarations
Conflict of interest
Authors have no conflict of interest.
Ethical approval
This study was undertaken through prior approval from the Institutional Animal Ethics Committee (IAEC) of KIET school of Pharmacy (KSOP), Ghaziabad, India, as per standard guidelines of the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA) with approval number- IAEC/KSOP/2020-21/15.
Informed consent
This article does not contain any studies with human participants.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ibrahim, I.M., Alsieni, M., Almalki, S.G. et al. Comparative evaluation of natural neuroprotectives and their combinations on chronic immobilization stress-induced depression in experimental mice. 3 Biotech 13, 22 (2023). https://doi.org/10.1007/s13205-022-03438-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s13205-022-03438-2