The Role of Natural Products in Treatment of Depressive Disorder

Tayebeh      Noori; Antoni      Sureda; Eduardo      Sobarzo-Sánchez; Samira      Shirooie
doi:10.2174/1570159X20666220103140834
Abstract

Depressive disorder is one of the most common psychiatric syndromes that, if left untreated, can cause many disturbances in a person's life. Numerous factors are involved in depression, including inflammation, brain-derived neurotrophic factor (BDNF), GABAergic system, hypothalamic– pituitary–adrenal (HPA) Axis, monoamine neurotransmitters (serotonin (5-HT), noradrenaline, and dopamine). Common treatments for depression are selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, but these drugs have several side effects such as anxiety, diarrhea, constipation, weight loss, and sexual dysfunctions. These agents only reduce the symptoms and temporarily reduce the rate of cognitive impairment associated with depression. As a result, extensive research has recently been conducted on the potential use of antidepressant and sedative herbs. According to the available data, herbs used in traditional medicine can be significantly effective in reducing depression, depressive symptoms and improving patients' performance. The present study provides a summary of biomarkers and therapeutic goals of depression and shows that natural products such as saffron or genipin have antidepressant effects. Some of the useful natural products and their mechanisms were evaluated. Data on various herbs and natural isolated compounds reported to prevent and reduce depressive symptoms is also discussed.
Keywords: Depression, natural products, BDNF, HPA axis, monoamine neurotransmitters, depressive symptoms.
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[1] 
Zhou, H.; Polimanti, R.; Yang, B.Z.; Wang, Q.; Han, S.; Sherva, R.; Nuñez, Y.Z.; Zhao, H.; Farrer, L.A.; Kranzler, H.R.; Gelernter, J. Genetic risk variants associated with comorbid alcohol dependence and major depression. JAMA Psychiatry,  2017, 74(12), 1234-1241.
[http://dx.doi.org/10.1001/jamapsychiatry.2017.3275] [PMID:  29071344] 
[2] 
Gururajan, A.; Reif, A.; Cryan, J.F.; Slattery, D.A. The future of rodent models in depression research. Nat. Rev. Neurosci.,  2019, 20(11), 686-701.
[http://dx.doi.org/10.1038/s41583-019-0221-6] [PMID:  31578460] 
[3] 
Franzoni, L.; Stein, R. Moderate exercise improves depressive symptoms and pain in elderly people. Int. J. Cardiovasc. Sci., 2019.
[4] 
LeMoult, J.; Gotlib, I.H. Depression: A cognitive perspective. Clin. Psychol. Rev.,  2019, 69, 51-66.
[http://dx.doi.org/10.1016/j.cpr.2018.06.008] [PMID:  29961601] 
[5] 
Ahern, E.; Semkovska, M. Cognitive functioning in the first-episode of major depressive disorder: A systematic review and meta-analysis. Neuropsychology,  2017, 31(1), 52-72.
[http://dx.doi.org/10.1037/neu0000319] [PMID:  27732039] 
[6] 
Chakrabarty, T.; Hadjipavlou, G.; Lam, R.W. Cognitive dysfunction in major depressive disorder: Assessment, impact, and management. Focus Am. Psychiatr. Publ.,  2016, 14(2), 194-206.
[http://dx.doi.org/10.1176/appi.focus.20150043] [PMID:  31975803] 
[7] 
Liezmann, C.; Klapp, B.; Peters, E.M. Stress, atopy and allergy: A re-evaluation from a psychoneuroimmunologic persepective. Dermatoendocrinol,  2011, 3(1), 37-40.
[http://dx.doi.org/10.4161/derm.3.1.14618] [PMID:  21519408] 
[8] 
Celano, C.M.; Huffman, J.C. Depression and cardiac disease: A review. Cardiology,  2011, 19(3), 130-142.
[PMID:  21464641] 
[9] 
Shelton, R.C.; Miller, A.H. Inflammation in depression: Is adiposity a cause? Dialogues Clin. Neurosci.,  2011, 13(1), 41-53.
[http://dx.doi.org/10.31887/DCNS.2011.13.1/rshelton] [PMID:  21485745] 
[10] 
Kubera, M.; Obuchowicz, E.; Goehler, L.; Brzeszcz, J.; Maes, M. In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(3), 744-759.
[http://dx.doi.org/10.1016/j.pnpbp.2010.08.026] [PMID:  20828592] 
[11] 
Fathinezhad, Z.; Sewell, R.D.E.; Lorigooini, Z.; Rafieian-Kopaei, M. Depression and treatment with effective herbs. Curr. Pharm. Des.,  2019, 25(6), 738-745.
[http://dx.doi.org/10.2174/1381612825666190402105803] [PMID:  30947651] 
[12] 
Martino, M.; Rocchi, G.; Escelsior, A.; Contini, P.; Colicchio, S.; de Berardis, D.; Amore, M.; Fornaro, P.; Fornaro, M. NGF serum levels variations in major depressed patients receiving duloxetine. Psychoneuroendocrinology,  2013, 38(9), 1824-1828.
[http://dx.doi.org/10.1016/j.psyneuen.2013.02.009] [PMID:  23507186] 
[13] 
Anderson, I.M.; Nutt, D.J.; Deakin, J.F. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 1993 British Association for Psychopharmacology guidelines. J. Psychopharmacol.,  2000, 14(1), 3-20.
[http://dx.doi.org/10.1177/026988110001400101] [PMID:  10757248] 
[14] 
Takayanagi, Y. Antidepressant use and lifetime history of mental disorders in a community sample: Results from the Baltimore epidemiologic catchment area study. J. Clin. Psychiatry,  2014, 76(1), 40-44.
[15] 
Gartlehner, G. Drug class review: Second-generation antidepressants: Final update 5 report. 2011.
[16] 
MacQueen, G.; Santaguida, P.; Keshavarz, H.; Jaworska, N.; Levine, M.; Beyene, J.; Raina, P. Systematic review of clinical practice guidelines for failed antidepressant treatment response in major depressive disorder, dysthymia, and subthreshold depression in adults. Can. J. Psychiatry,  2017, 62(1), 11-23.
[http://dx.doi.org/10.1177/0706743716664885] [PMID:  27554483] 
[17] 
Jantan, I. The evolving role of natural products from the tropical rainforests as a replenishable source of new drug leads.  Drug Discov. Devel. Mol. Med.,  2015, 3-38.
[http://dx.doi.org/10.5772/59603] 
[18] 
Nabavi, S.M.; Daglia, M.; Braidy, N.; Nabavi, S.F. Natural products, micronutrients, and nutraceuticals for the treatment of depression: A short review. Nutr. Neurosci.,  2017, 20(3), 180-194.
[http://dx.doi.org/10.1080/1028415X.2015.1103461] [PMID:  26613119] 
[19] 
Zunszain, P.A.; Hepgul, N.; Pariante, C.M. Inflammation and depression. Behavioral neurobiology of depression and its treatment,,  2012, 135-151.
[http://dx.doi.org/10.1007/7854_2012_211] 
[20] 
Raza, M.U.; Tufan, T.; Wang, Y.; Hill, C.; Zhu, M.Y. DNA damage in major psychiatric diseases. Neurotox. Res.,  2016, 30(2), 251-267.
[http://dx.doi.org/10.1007/s12640-016-9621-9] [PMID:  27126805] 
[21] 
Krishnadas, R.; Cavanagh, J. Depression: An inflammatory illness? J. Neurol. Neurosurg. Psychiatry,  2012, 83(5), 495-502.
[http://dx.doi.org/10.1136/jnnp-2011-301779] [PMID:  22423117] 
[22] 
Kiecolt-Glaser, J.K.; Derry, H.M.; Fagundes, C.P. Inflammation: Depression fans the flames and feasts on the heat. Am. J. Psychiatry,  2015, 172(11), 1075-1091.
[http://dx.doi.org/10.1176/appi.ajp.2015.15020152] [PMID:  26357876] 
[23] 
Raison, C.L.; Miller, A.H. Is depression an inflammatory disorder? Curr. Psychiatry Rep.,  2011, 13(6), 467-475.
[http://dx.doi.org/10.1007/s11920-011-0232-0] [PMID:  21927805] 
[24] 
Glassman, A.H.; Miller, G.E. Where there is depression, there is inflammation... sometimes! Biol. Psychiatry,  2007, 62(4), 280-281.
[25] 
Allison, D.J.; Ditor, D.S. The common inflammatory etiology of depression and cognitive impairment: A therapeutic target. J. Neuroinflammation,  2014, 11(1), 151.
[http://dx.doi.org/10.1186/s12974-014-0151-1] [PMID:  25178630] 
[26] 
Howren, M.B.; Lamkin, D.M.; Suls, J. Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis. Psychosom. Med.,  2009, 71(2), 171-186.
[http://dx.doi.org/10.1097/PSY.0b013e3181907c1b] [PMID:  19188531] 
[27] 
Maes, M.; Bosmans, E.; De Jongh, R.; Kenis, G.; Vandoolaeghe, E.; Neels, H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine,  1997, 9(11), 853-858.
[http://dx.doi.org/10.1006/cyto.1997.0238] [PMID:  9367546] 
[28] 
Haapakoski, R.; Mathieu, J.; Ebmeier, K.P.; Alenius, H.; Kivimäki, M. Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain Behav. Immun.,  2015, 49, 206-215.
[http://dx.doi.org/10.1016/j.bbi.2015.06.001] [PMID:  26065825] 
[29] 
De Berardis, D.; Campanella, D.; Gambi, F.; La Rovere, R.; Carano, A.; Conti, C.M.; Sivestrini, C.; Serroni, N.; Piersanti, D.; Di Giuseppe, B.; Moschetta, F.S.; Cotellessa, C.; Fulcheri, M.; Salerno, R.M.; Ferro, F.M. The role of C-reactive protein in mood disorders. Int. J. Immunopathol. Pharmacol.,  2006, 19(4), 721-725.
[http://dx.doi.org/10.1177/039463200601900402] [PMID:  17166394] 
[30] 
Felger, J.C.; Haroon, E.; Patel, T.A.; Goldsmith, D.R.; Wommack, E.C.; Woolwine, B.J.; Le, N.A.; Feinberg, R.; Tansey, M.G.; Miller, A.H. What does plasma CRP tell us about peripheral and central inflammation in depression? Mol. Psychiatry,  2020, 25(6), 1301-1311.
[http://dx.doi.org/10.1038/s41380-018-0096-3] [PMID:  29895893] 
[31] 
Duivis, H.E.; Vogelzangs, N.; Kupper, N.; de Jonge, P.; Penninx, B.W. Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the netherlands study of depression and anxiety (NESDA). Psychoneuroendocrinology,  2013, 38(9), 1573-1585.
[http://dx.doi.org/10.1016/j.psyneuen.2013.01.002] [PMID:  23399050] 
[32] 
Lamers, F.; Vogelzangs, N.; Merikangas, K.R.; de Jonge, P.; Beekman, A.T.; Penninx, B.W. Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol. Psychiatry,  2013, 18(6), 692-699.
[http://dx.doi.org/10.1038/mp.2012.144] [PMID:  23089630] 
[33] 
Peirce, J.M.; Alviña, K. The role of inflammation and the gut microbiome in depression and anxiety. J. Neurosci. Res.,  2019, 97(10), 1223-1241.
[http://dx.doi.org/10.1002/jnr.24476] [PMID:  31144383] 
[34] 
De Berardis, D.; Fornaro, M.; Orsolini, L.; Iasevoli, F.; Tomasetti, C.; de Bartolomeis, A.; Serroni, N.; De Lauretis, I.; Girinelli, G.; Mazza, M.; Valchera, A.; Carano, A.; Vellante, F.; Matarazzo, I.; Perna, G.; Martinotti, G.; Di Giannantonio, M. Effect of agomelatine treatment on C-reactive protein levels in patients with major depressive disorder: An exploratory study in “real-world,” everyday clinical practice. CNS Spectr.,  2017, 22(4), 342-347.
[http://dx.doi.org/10.1017/S1092852916000572] [PMID:  27702411] 
[35] 
Anderson, G. Editorial: The Kynurenine and Melatonergic Pathways in Psychiatric and CNS Disorders. Curr. Pharm. Des.,  2016, 22(8), 947-948.
[http://dx.doi.org/10.2174/1381612822999160104143932] [PMID:  26725229] 
[36] 
Bo, L.; Guojun, T.; Li, G. An Expanded Neuroimmunomodulation Axis: sCD83-Indoleamine 2,3-Dioxygenase-kynurenine pathway and updates of kynurenine pathway in neurologic diseases. Front. Immunol.,  2018, 9, 1363.
[http://dx.doi.org/10.3389/fimmu.2018.01363] [PMID:  29963055] 
[37] 
Gałecki, P.; Talarowska, M. Inflammatory theory of depression. Psychiatr. Pol.,  2018, 52(3), 437-447.
[http://dx.doi.org/10.12740/PP/76863] [PMID:  30218560] 
[38] 
Lamers, F.; Milaneschi, Y.; de Jonge, P.; Giltay, E.J.; Penninx, B.W.J.H. Metabolic and inflammatory markers: Associations with individual depressive symptoms. Psychol. Med.,  2018, 48(7), 1102-1110.
[http://dx.doi.org/10.1017/S0033291717002483] [PMID:  28889804] 
[39] 
Black, C.; Miller, B.J. Meta-analysis of cytokines and chemokines in suicidality: Distinguishing suicidal versus nonsuicidal patients. Biol. Psychiatry,  2015, 78(1), 28-37.
[http://dx.doi.org/10.1016/j.biopsych.2014.10.014] [PMID:  25541493] 
[40] 
De Berardis, D.; Conti, C.M.; Serroni, N.; Moschetta, F.S.; Olivieri, L.; Carano, A.; Salerno, R.M.; Cavuto, M.; Farina, B.; Alessandrini, M.; Janiri, L.; Pozzi, G.; Di Giannantonio, M. The effect of newer serotonin-noradrenalin antidepressants on cytokine production: A review of the current literature. Int. J. Immunopathol. Pharmacol.,  2010, 23(2), 417-422.
[http://dx.doi.org/10.1177/039463201002300204] [PMID:  20646337] 
[41] 
Castrén, E. Neurotrophins and psychiatric disorders. Handb. Exp. Pharmacol.,  2014, 220, 461-479.
[http://dx.doi.org/10.1007/978-3-642-45106-5_17] [PMID:  24668483] 
[42] 
Park, H.; Poo, M.M. Neurotrophin regulation of neural circuit development and function. Nat. Rev. Neurosci.,  2013, 14(1), 7-23.
[http://dx.doi.org/10.1038/nrn3379] [PMID:  23254191] 
[43] 
Yang, T.; Nie, Z.; Shu, H.; Kuang, Y.; Chen, X.; Cheng, J.; Yu, S.; Liu, H. The role of BDNF on neural plasticity in depression. Front. Cell. Neurosci.,  2020, 14, 82.
[http://dx.doi.org/10.3389/fncel.2020.00082] [PMID:  32351365] 
[44] 
Molteni, R.; Calabrese, F.; Racagni, G.; Fumagalli, F.; Riva, M.A. Antipsychotic drug actions on gene modulation and signaling mechanisms. Pharmacol. Ther.,  2009, 124(1), 74-85.
[http://dx.doi.org/10.1016/j.pharmthera.2009.06.001] [PMID:  19540875] 
[45] 
Calabrese, F.; Molteni, R.; Riva, M.A. Antistress properties of antidepressant drugs and their clinical implications. Pharmacol. Ther.,  2011, 132(1), 39-56.
[http://dx.doi.org/10.1016/j.pharmthera.2011.05.007] [PMID:  21640755] 
[46] 
Björkholm, C.; Monteggia, L.M. BDNF - a key transducer of antidepressant effects. Neuropharmacology,  2016, 102, 72-79.
[http://dx.doi.org/10.1016/j.neuropharm.2015.10.034] [PMID:  26519901] 
[47] 
Barde, Y-A.; Edgar, D.; Thoenen, H. Purification of a new neurotrophic factor from mammalian brain. EMBO J.,  1982, 1(5), 549-553.
[http://dx.doi.org/10.1002/j.1460-2075.1982.tb01207.x] [PMID:  7188352] 
[48] 
De Berardis, D. A comprehensive review on the efficacy of Sadenosyl- L-methionine in major depressive disorder. CNS and Neurological Disorders-Drug Targets (Formerly Current Drug Targets- CNS and Neurological Disorders) 2016, 15(1), 34-44.
[http://dx.doi.org/10.2174/1871527314666150821103825] 
[49] 
Martinotti, G.; Pettorruso, M.; De Berardis, D.; Varasano, P.A.; Lucidi Pressanti, G.; De Remigis, V.; Valchera, A.; Ricci, V.; Di Nicola, M.; Janiri, L.; Biggio, G.; Di Giannantonio, M. Agomelatine increases BDNF serum levels in depressed patients in correlation with the improvement of depressive symptoms. Int. J. Neuropsychopharmacol.,  2016, 19(5), pyw003.
[http://dx.doi.org/10.1093/ijnp/pyw003] [PMID:  26775293] 
[50] 
Guillin, O.; Demily, C.; Thibaut, F. Brain-derived neurotrophic factor in schizophrenia and its relation with dopamine. Int. Rev. Neurobiol.,  2007, 78, 377-395.
[http://dx.doi.org/10.1016/S0074-7742(06)78012-6] [PMID:  17349867] 
[51] 
Zou, L.; Xue, Y.; Jones, M.; Heinbockel, T.; Ying, M.; Zhan, X. The effects of quinine on neurophysiological properties of dopaminergic neurons. Neurotox. Res.,  2018, 34(1), 62-73.
[http://dx.doi.org/10.1007/s12640-017-9855-1] [PMID:  29285614] 
[52] 
Favalli, G.; Li, J.; Belmonte-de-Abreu, P.; Wong, A.H.; Daskalakis, Z.J. The role of BDNF in the pathophysiology and treatment of schizophrenia. J. Psychiatr. Res.,  2012, 46(1), 1-11.
[http://dx.doi.org/10.1016/j.jpsychires.2011.09.022] [PMID:  22030467] 
[53] 
Hasbi, A.; Fan, T.; Alijaniaram, M.; Nguyen, T.; Perreault, M.L.; O’Dowd, B.F.; George, S.R. Calcium signaling cascade links dopamine D1-D2 receptor heteromer to striatal BDNF production and neuronal growth. Proc. Natl. Acad. Sci. USA,  2009, 106(50), 21377-21382.
[http://dx.doi.org/10.1073/pnas.0903676106] [PMID:  19948956] 
[54] 
Peng, S.; Li, W.; Lv, L.; Zhang, Z.; Zhan, X. BDNF as a biomarker in diagnosis and evaluation of treatment for schizophrenia and depression. Discov. Med.,  2018, 26(143), 127-136.
[PMID:  30586536] 
[55] 
Woo, N.H.; Teng, H.K.; Siao, C.J.; Chiaruttini, C.; Pang, P.T.; Milner, T.A.; Hempstead, B.L.; Lu, B. Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat. Neurosci.,  2005, 8(8), 1069-1077.
[http://dx.doi.org/10.1038/nn1510] [PMID:  16025106] 
[56] 
Remy, P.; Doder, M.; Lees, A.; Turjanski, N.; Brooks, D. Depression in Parkinson’s disease: Loss of dopamine and noradrenaline innervation in the limbic system. Brain,  2005, 128(Pt 6), 1314-1322.
[http://dx.doi.org/10.1093/brain/awh445] [PMID:  15716302] 
[57] 
Aggio, V.P. 3.025 Brain-derived neurotrophic factor associates with gray matter volumes and early adverse experiences in bipolar disorder. Eur. Neuropsychopharmacol.,  2016, 1(26), S68-S69.
[http://dx.doi.org/10.1016/S0924-977X(16)70075-7] 
[58] 
Nase, S.; Köhler, S.; Jennebach, J.; Eckert, A.; Schweinfurth, N.; Gallinat, J.; Lang, U.E.; Kühn, S. Role of serum brain derived neurotrophic factor and central n-acetylaspartate for clinical response under antidepressive pharmacotherapy. Neurosignals,  2016, 24(1), 1-14.
[http://dx.doi.org/10.1159/000442607] [PMID:  26859851] 
[59] 
Froestl, W. An historical perspective on GABAergic drugs. Future Med. Chem.,  2011, 3(2), 163-175.
[http://dx.doi.org/10.4155/fmc.10.285] [PMID:  21428811] 
[60] 
Losi, G.; Mariotti, L.; Carmignoto, G. GABAergic interneuron to astrocyte signalling: A neglected form of cell communication in the brain. Philos. Trans. R. Soc. Lond. B Biol. Sci.,  2014, 369(1654), 20130609.
[http://dx.doi.org/10.1098/rstb.2013.0609] [PMID:  25225102] 
[61] 
Maffei, A.; Charrier, C.; Caiati, M.D.; Barberis, A.; Mahadevan, V.; Woodin, M.A.; Tyagarajan, S.K. Emerging mechanisms underlying dynamics of GABAergic synapses. J. Neurosci.,  2017, 37(45), 10792-10799.
[http://dx.doi.org/10.1523/JNEUROSCI.1824-17.2017] [PMID:  29118207] 
[62] 
Rudolph, U.; Möhler, H. GABAA receptor subtypes: Therapeutic potential in Down syndrome, affective disorders, schizophrenia, and autism. Annu. Rev. Pharmacol. Toxicol.,  2014, 54, 483-507.
[http://dx.doi.org/10.1146/annurev-pharmtox-011613-135947] [PMID:  24160694] 
[63] 
Möhler, H. GABAA receptors in central nervous system disease: Anxiety, epilepsy, and insomnia. J. Recept. Signal Transduct. Res.,  2006, 26(5-6), 731-740.
[http://dx.doi.org/10.1080/10799890600920035] [PMID:  17118808] 
[64] 
Brown, E.S.; Varghese, F.P.; McEwen, B.S. Association of depression with medical illness: Does cortisol play a role? Biol. Psychiatry,  2004, 55(1), 1-9.
[http://dx.doi.org/10.1016/S0006-3223(03)00473-6] [PMID:  14706419] 
[65] 
Luhmann, H.J.; Kral, T.; Heinemann, U. Influence of hypoxia on excitation and GABAergic inhibition in mature and developing rat neocortex. Exp. Brain Res.,  1993, 97(2), 209-224.
[http://dx.doi.org/10.1007/BF00228690] [PMID:  7908647] 
[66] 
Lissemore, J.I.; Bhandari, A.; Mulsant, B.H.; Lenze, E.J.; Reynolds, C.F., III; Karp, J.F.; Rajji, T.K.; Noda, Y.; Zomorrodi, R.; Sibille, E.; Daskalakis, Z.J.; Blumberger, D.M. Reduced GABAergic cortical inhibition in aging and depression. Neuropsychopharmacology,  2018, 43(11), 2277-2284.
[http://dx.doi.org/10.1038/s41386-018-0093-x] [PMID:  29849055] 
[67] 
Banasr, M.; Lepack, A.; Fee, C.; Duric, V.; Maldonado-Aviles, J.; DiLeone, R.; Sibille, E.; Duman, R.S.; Sanacora, G. Characterization of GABAergic marker expression in the chronic unpredictable stress model of depression. Chronic Stress (Thousand Oaks),  2017, 1, 2470547017720459.
[http://dx.doi.org/10.1177/2470547017720459] [PMID:  28835932] 
[68] 
Duman, R.S.; Sanacora, G.; Krystal, J.H. Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron,  2019, 102(1), 75-90.
[http://dx.doi.org/10.1016/j.neuron.2019.03.013] [PMID:  30946828] 
[69] 
Keller, J.; Gomez, R.; Williams, G.; Lembke, A.; Lazzeroni, L.; Murphy, G.M., Jr; Schatzberg, A.F. HPA axis in major depression: Cortisol, clinical symptomatology and genetic variation predict cognition. Mol. Psychiatry,  2017, 22(4), 527-536.
[http://dx.doi.org/10.1038/mp.2016.120] [PMID:  27528460] 
[70] 
Stetler, C.; Miller, G.E. Depression and hypothalamic-pituitary-adrenal activation: A quantitative summary of four decades of research. Psychosom. Med.,  2011, 73(2), 114-126.
[http://dx.doi.org/10.1097/PSY.0b013e31820ad12b] [PMID:  21257974] 
[71] 
Zunszain, P.A.; Anacker, C.; Cattaneo, A.; Carvalho, L.A.; Pariante, C.M. Glucocorticoids, cytokines and brain abnormalities in depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(3), 722-729.
[http://dx.doi.org/10.1016/j.pnpbp.2010.04.011] [PMID:  20406665] 
[72] 
Pariante, C.M.; Lightman, S.L. The HPA axis in major depression: Classical theories and new developments. Trends Neurosci.,  2008, 31(9), 464-468.
[http://dx.doi.org/10.1016/j.tins.2008.06.006] [PMID:  18675469] 
[73] 
Belvederi Murri, M.; Pariante, C.; Mondelli, V.; Masotti, M.; Atti, A.R.; Mellacqua, Z.; Antonioli, M.; Ghio, L.; Menchetti, M.; Zanetidou, S.; Innamorati, M.; Amore, M. HPA axis and aging in depression: Systematic review and meta-analysis. Psychoneuroendocrinology,  2014, 41, 46-62.
[http://dx.doi.org/10.1016/j.psyneuen.2013.12.004] [PMID:  24495607] 
[74] 
de Rezende, M.G.; Garcia-Leal, C.; de Figueiredo, F.P.; Cavalli, R.C.; Spanghero, M.S.; Barbieri, M.A.; Bettiol, H.; de Castro, M.; Del-Ben, C.M. Altered functioning of the HPA axis in depressed postpartum women. J. Affect. Disord.,  2016, 193, 249-256.
[http://dx.doi.org/10.1016/j.jad.2015.12.065] [PMID:  26773916] 
[75] 
Anacker, C.; Zunszain, P.A.; Carvalho, L.A.; Pariante, C.M. The glucocorticoid receptor: Pivot of depression and of antidepressant treatment? Psychoneuroendocrinology,  2011, 36(3), 415-425.
[http://dx.doi.org/10.1016/j.psyneuen.2010.03.007] [PMID:  20399565] 
[76] 
Bosker, F.J.; Westerink, B.H.; Cremers, T.I.; Gerrits, M.; van der Hart, M.G.; Kuipers, S.D.; van der Pompe, G.; ter Horst, G.J.; den Boer, J.A.; Korf, J. Future antidepressants: What is in the pipeline and what is missing? CNS Drugs,  2004, 18(11), 705-732.
[http://dx.doi.org/10.2165/00023210-200418110-00002] [PMID:  15330686] 
[77] 
Von Werne Baes, C.; de Carvalho Tofoli, S.M.; Martins, C.M.; Juruena, M.F. Assessment of the hypothalamic-pituitary-adrenal axis activity: Glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress - a systematic review. Acta Neuropsychiatr.,  2012, 24(1), 4-15.
[http://dx.doi.org/10.1111/j.1601-5215.2011.00610.x] [PMID:  28183380] 
[78] 
Juruena, M.F. Early-life stress and HPA axis trigger recurrent adulthood depression. Epilepsy Behav.,  2014, 38, 148-159.
[http://dx.doi.org/10.1016/j.yebeh.2013.10.020] [PMID:  24269030] 
[79] 
Seo, J-S.; Zhong, P.; Liu, A.; Yan, Z.; Greengard, P. Elevation of p11 in lateral habenula mediates depression-like behavior. Mol. Psychiatry,  2018, 23(5), 1113-1119.
[http://dx.doi.org/10.1038/mp.2017.96] [PMID:  28507317] 
[80] 
Sartorius, A. Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol. Psychiatry,  2010, 67(2), 9-11.
[http://dx.doi.org/10.1016/j.biopsych.2009.08.027] 
[81] 
Li, B.; Piriz, J.; Mirrione, M.; Chung, C.; Proulx, C.D.; Schulz, D.; Henn, F.; Malinow, R. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature,  2011, 470(7335), 535-539.
[http://dx.doi.org/10.1038/nature09742] [PMID:  21350486] 
[82] 
Li, K. βCaMKII in lateral habenula mediates core symptoms of depression. Science,  2013, 341(6149), 1016-1020.
[83] 
Sartorius, A.; Henn, F.A. Deep brain stimulation of the lateral habenula in treatment resistant major depression. Med. Hypotheses,  2007, 69(6), 1305-1308.
[http://dx.doi.org/10.1016/j.mehy.2007.03.021] [PMID:  17498883] 
[84] 
Proulx, C.D.; Hikosaka, O.; Malinow, R. Reward processing by the lateral habenula in normal and depressive behaviors. Nat. Neurosci.,  2014, 17(9), 1146-1152.
[http://dx.doi.org/10.1038/nn.3779] [PMID:  25157511] 
[85] 
Stamatakis, A.M.; Van Swieten, M.; Basiri, M.L.; Blair, G.A.; Kantak, P.; Stuber, G.D. Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward. J. Neurosci.,  2016, 36(2), 302-311.
[http://dx.doi.org/10.1523/JNEUROSCI.1202-15.2016] [PMID:  26758824] 
[86] 
Warden, M.R.; Selimbeyoglu, A.; Mirzabekov, J.J.; Lo, M.; Thompson, K.R.; Kim, S.Y.; Adhikari, A.; Tye, K.M.; Frank, L.M.; Deisseroth, K. A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature,  2012, 492(7429), 428-432.
[http://dx.doi.org/10.1038/nature11617] [PMID:  23160494] 
[87] 
Margolis, E.B.; Fields, H.L. Mu opioid receptor actions in the lateral habenula. PLoS One,  2016, 11(7), e0159097.
[http://dx.doi.org/10.1371/journal.pone.0159097] [PMID:  27427945] 
[88] 
Lecourtier, L.; Kelly, P.H. A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition. Neurosci. Biobehav. Rev.,  2007, 31(5), 658-672.
[http://dx.doi.org/10.1016/j.neubiorev.2007.01.004] [PMID:  17379307] 
[89] 
Shelton, L.; Pendse, G.; Maleki, N.; Moulton, E.A.; Lebel, A.; Becerra, L.; Borsook, D. Mapping pain activation and connectivity of the human habenula. J. Neurophysiol.,  2012, 107(10), 2633-2648.
[http://dx.doi.org/10.1152/jn.00012.2012] [PMID:  22323632] 
[90] 
Boulos, L-J.; Darcq, E.; Kieffer, B.L. Translating the habenula—from rodents to humans. Biol. Psychiatry,  2017, 81(4), 296-305.
[http://dx.doi.org/10.1016/j.biopsych.2016.06.003] [PMID:  27527822] 
[91] 
Kraus, C.; Castrén, E.; Kasper, S.; Lanzenberger, R. Serotonin and neuroplasticity - Links between molecular, functional and structural pathophysiology in depression. Neurosci. Biobehav. Rev.,  2017, 77, 317-326.
[http://dx.doi.org/10.1016/j.neubiorev.2017.03.007] [PMID:  28342763] 
[92] 
Guirado, R.; Perez-Rando, M.; Sanchez-Matarredona, D.; Castrén, E.; Nacher, J. Chronic fluoxetine treatment alters the structure, connectivity and plasticity of cortical interneurons. Int. J. Neuropsychopharmacol.,  2014, 17(10), 1635-1646.
[http://dx.doi.org/10.1017/S1461145714000406] [PMID:  24786752] 
[93] 
Varea, E.; Blasco-Ibáñez, J.M.; Gómez-Climent, M.A.; Castillo-Gómez, E.; Crespo, C.; Martínez-Guijarro, F.J.; Nácher, J. Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial prefrontal cortex. Neuropsychopharmacology,  2007, 32(4), 803-812.
[http://dx.doi.org/10.1038/sj.npp.1301183] [PMID:  16900104] 
[94] 
Mondanelli, G.; Volpi, C. Serotonin Pathway in Neuroimmune Network.  In: in Serotonin and the CNS-New Developments in Pharmacology and Therapeutics; IntechOpen, 2021. 
[http://dx.doi.org/10.5772/intechopen.96733] 
[95] 
Bakshi, A.; Tadi, P. Biochemistry, Serotonin; StatPearls, 2021. 
[96] 
Żmudzka, E.; Sałaciak, K.; Sapa, J.; Pytka, K. Serotonin receptors in depression and anxiety: Insights from animal studies. Life Sci.,  2018, 210, 106-124.
[http://dx.doi.org/10.1016/j.lfs.2018.08.050] [PMID:  30144453] 
[97] 
Gijsman, H.J.; Geddes, J.R.; Rendell, J.M.; Nolen, W.A.; Goodwin, G.M. Antidepressants for bipolar depression: A systematic review of randomized, controlled trials. Am. J. Psychiatry,  2004, 161(9), 1537-1547.
[http://dx.doi.org/10.1176/appi.ajp.161.9.1537] [PMID:  15337640] 
[98] 
Kurita, M. Noradrenaline plays a critical role in the switch to a manic episode and treatment of a depressive episode. Neuropsychiatr. Dis. Treat.,  2016, 12, 2373-2380.
[http://dx.doi.org/10.2147/NDT.S109835] [PMID:  27703355] 
[99] 
Moraga-Amaro, R.; Gonzalez, H.; Pacheco, R.; Stehberg, J. Dopamine receptor D3 deficiency results in chronic depression and anxiety. Behav. Brain Res.,  2014, 274, 186-193.
[http://dx.doi.org/10.1016/j.bbr.2014.07.055] [PMID:  25110304] 
[100] 
Belujon, P.; Grace, A.A. Dopamine system dysregulation in major depressive disorders. Int. J. Neuropsychopharmacol.,  2017, 20(12), 1036-1046.
[http://dx.doi.org/10.1093/ijnp/pyx056] [PMID:  29106542] 
[101] 
Dunlop, B.W.; Nemeroff, C.B. The role of dopamine in the pathophysiology of depression. Arch. Gen. Psychiatry,  2007, 64(3), 327-337.
[http://dx.doi.org/10.1001/archpsyc.64.3.327] [PMID:  17339521] 
[102] 
Li, Y.; Zhu, Z.R.; Ou, B.C.; Wang, Y.Q.; Tan, Z.B.; Deng, C.M.; Gao, Y.Y.; Tang, M.; So, J.H.; Mu, Y.L.; Zhang, L.Q. Dopamine D2/D3 but not dopamine D1 receptors are involved in the rapid antidepressant-like effects of ketamine in the forced swim test. Behav. Brain Res.,  2015, 279, 100-105.
[http://dx.doi.org/10.1016/j.bbr.2014.11.016] [PMID:  25449845] 
[103] 
Szafrański, T. Herbal remedies in depression--state of the art. Psychiatr. Pol.,  2014, 48(1), 59-73.
[http://dx.doi.org/10.12740/PP/21865] [PMID:  24946435] 
[104] 
Pohl, F.; Kong Thoo Lin, P. The potential use of plant natural products and plant extracts with antioxidant properties for the prevention/treatment of neurodegenerative diseases: In vitro, in vivo and clinical trials. Molecules,  2018, 23(12), 3283.
[http://dx.doi.org/10.3390/molecules23123283] [PMID:  30544977] 
[105] 
Bruni, O.; Ferini-Strambi, L.; Giacomoni, E.; Pellegrino, P. Herbal remedies and their possible effect on the GABAergic system and sleep. Nutrients,  2021, 13(2), 530.
[http://dx.doi.org/10.3390/nu13020530] [PMID:  33561990] 
[106] 
Rai, D.; Bhatia, G.; Palit, G.; Pal, R.; Singh, S.; Singh, H.K. Adaptogenic effect of Bacopa monniera (Brahmi). Pharmacol. Biochem. Behav.,  2003, 75(4), 823-830.
[http://dx.doi.org/10.1016/S0091-3057(03)00156-4] [PMID:  12957224] 
[107] 
Novío, S.; Núñez, M.J.; Amigo, G.; Freire-Garabal, M. Effects of fluoxetine on the oxidative status of peripheral blood leucocytes of restraint-stressed mice. Basic Clin. Pharmacol. Toxicol.,  2011, 109(5), 365-371.
[http://dx.doi.org/10.1111/j.1742-7843.2011.00736.x] [PMID:  21624059] 
[108] 
Rabiei, Z.; Rabiei, S. A review on antidepressant effect of medicinal plants. Bangladesh J. Pharmacol.,  2017, 12(1), 1-11.
[http://dx.doi.org/10.3329/bjp.v12i1.29184] 
[109] 
Li, R.; Wang, X.; Qin, T.; Qu, R.; Ma, S. Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain. Behav. Brain Res.,  2016, 296, 318-325.
[http://dx.doi.org/10.1016/j.bbr.2015.09.031] [PMID:  26416673] 
[110] 
Nabavi, S.F.; Khan, H.; D’onofrio, G.; Šamec, D.; Shirooie, S.; Dehpour, A.R.; Argüelles, S.; Habtemariam, S.; Sobarzo-Sanchez, E. Apigenin as neuroprotective agent: Of mice and men. Pharmacol. Res.,  2018, 128, 359-365.
[http://dx.doi.org/10.1016/j.phrs.2017.10.008] [PMID:  29055745] 
[111] 
Li, F. Apigenin alleviates endotoxin-induced myocardial toxicity by modulating inflammation, oxidative stress, and autophagy. Oxid. Med. Cell. Longev.,  2017, 2017, 2302896.
[http://dx.doi.org/10.1155/2017/2302896] 
[112] 
Soyman, Z.; Kelekçi, S.; Sal, V.; Şevket, O.; Bayındır, N.; Uzun, H. Effects of apigenin on experimental ischemia/reperfusion injury in the rat ovary. Balkan Med. J.,  2017, 34(5), 444-449.
[http://dx.doi.org/10.4274/balkanmedj.2016.1386] [PMID:  28443590] 
[113] 
Salehi, B.; Venditti, A.; Sharifi-Rad, M.; Kręgiel, D.; Sharifi-Rad, J.; Durazzo, A.; Lucarini, M.; Santini, A.; Souto, E.B.; Novellino, E.; Antolak, H.; Azzini, E.; Setzer, W.N.; Martins, N. The therapeutic potential of apigenin. Int. J. Mol. Sci.,  2019, 20(6), 1305.
[http://dx.doi.org/10.3390/ijms20061305] [PMID:  30875872] 
[114] 
Weng, L.; Guo, X.; Li, Y.; Yang, X.; Han, Y. Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice. Eur. J. Pharmacol.,  2016, 774, 50-54.
[http://dx.doi.org/10.1016/j.ejphar.2016.01.015] [PMID:  26826594] 
[115] 
Li, R.; Zhao, D.; Qu, R.; Fu, Q.; Ma, S. The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neurosci. Lett.,  2015, 594, 17-22.
[http://dx.doi.org/10.1016/j.neulet.2015.03.040] [PMID:  25800110] 
[116] 
Zhang, X.; Bu, H.; Jiang, Y.; Sun, G.; Jiang, R.; Huang, X.; Duan, H.; Huang, Z.; Wu, Q. The antidepressant effects of apigenin are associated with the promotion of autophagy via the mTOR/AMPK/ULK1 pathway. Mol. Med. Rep.,  2019, 20(3), 2867-2874.
[http://dx.doi.org/10.3892/mmr.2019.10491] [PMID:  31322238] 
[117] 
Yi, L-T.; Li, J.M.; Li, Y.C.; Pan, Y.; Xu, Q.; Kong, L.D. Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin. Life Sci.,  2008, 82(13-14), 741-751.
[http://dx.doi.org/10.1016/j.lfs.2008.01.007] [PMID:  18308340] 
[118] 
Shi, X. Baicalin attenuates subarachnoid hemorrhagic brain injury by modulating blood-brain barrier disruption, inflammation, and oxidative damage in mice. Oxid. Med. Cell. Longev.,  2017, 2017, 1401790.
[http://dx.doi.org/10.1155/2017/1401790] 
[119] 
Zhou, R.; Han, X.; Wang, J.; Sun, J. Baicalin may have a therapeutic effect in attention deficit hyperactivity disorder. Med. Hypotheses,  2015, 85(6), 761-764.
[http://dx.doi.org/10.1016/j.mehy.2015.10.012] [PMID:  26604025] 
[120] 
Li, Y-C.; Wang, L.L.; Pei, Y.Y.; Shen, J.D.; Li, H.B.; Wang, B.Y.; Bai, M. Baicalin decreases SGK1 expression in the hippocampus and reverses depressive-like behaviors induced by corticosterone. Neuroscience,  2015, 311, 130-137.
[http://dx.doi.org/10.1016/j.neuroscience.2015.10.023] [PMID:  26480816] 
[121] 
Li, Y-C.; Shen, J.D.; Li, J.; Wang, R.; Jiao, S.; Yi, L.T. Chronic treatment with baicalin prevents the chronic mild stress-induced depressive-like behavior: Involving the inhibition of cyclooxygenase-2 in rat brain. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2013, 40, 138-143.
[http://dx.doi.org/10.1016/j.pnpbp.2012.09.007] [PMID:  23022674] 
[122] 
Zuo, D.; Lin, L.; Liu, Y.; Wang, C.; Xu, J.; Sun, F.; Li, L.; Li, Z.; Wu, Y. Baicalin attenuates ketamine-induced neurotoxicity in the developing rats: Involvement of PI3K/Akt and CREB/BDNF/Bcl-2 pathways. Neurotox. Res.,  2016, 30(2), 159-172.
[http://dx.doi.org/10.1007/s12640-016-9611-y] [PMID:  26932180] 
[123] 
Miller, A.H.; Raison, C.L. The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat. Rev. Immunol.,  2016, 16(1), 22-34.
[http://dx.doi.org/10.1038/nri.2015.5] [PMID:  26711676] 
[124] 
Zhou, Z.Q.; Li, Y.L.; Ao, Z.B.; Wen, Z.L.; Chen, Q.W.; Huang, Z.G.; Xiao, B.; Yan, X.H. Baicalin protects neonatal rat brains against hypoxic-ischemic injury by upregulating glutamate transporter 1 via the phosphoinositide 3-kinase/protein kinase B signaling pathway. Neural Regen. Res.,  2017, 12(10), 1625-1631.
[http://dx.doi.org/10.4103/1673-5374.217335] [PMID:  29171427] 
[125] 
Zhang, K. Baicalin promotes hippocampal neurogenesis via SGK1-and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression. Sci. Rep.,  2016, 6(1), 1-9.
[http://dx.doi.org/10.1038/srep30951] [PMID:  28442746] 
[126] 
Lu, Y.; Sun, G.; Yang, F.; Guan, Z.; Zhang, Z.; Zhao, J.; Liu, Y.; Chu, L.; Pei, L. Baicalin regulates depression behavior in mice exposed to chronic mild stress via the Rac/LIMK/cofilin pathway. Biomed. Pharmacother.,  2019, 116, 109054.
[http://dx.doi.org/10.1016/j.biopha.2019.109054] [PMID:  31176122] 
[127] 
Zhong, J.; Li, G.; Xu, H.; Wang, Y.; Shi, M. Baicalin ameliorates chronic mild stress-induced depression-like behaviors in mice and attenuates inflammatory cytokines and oxidative stress. Braz. J. Med. Biol. Res.,  2019, 52(7), e8434.
[http://dx.doi.org/10.1590/1414-431x20198434] [PMID:  31241715] 
[128] 
Wang, W. Anti-cerebral ischemia/reperfusion mechanism of baicalin in rats. Zhongguo Shiyan Fangjixue Zazhi,  2016, 113-116.
[129] 
Liu, M-D.; Wu, H.; Wang, S.; Pang, P.; Jin, S.; Sun, C.F.; Liu, F.Y. MiR-1275 promotes cell migration, invasion and proliferation in squamous cell carcinoma of head and neck via up-regulating IGF-1R and CCR7. Gene,  2018, 646, 1-7.
[http://dx.doi.org/10.1016/j.gene.2017.12.049] [PMID:  29278769] 
[130] 
Peng, W-H.; Lo, K.L.; Lee, Y.H.; Hung, T.H.; Lin, Y.C. Berberine produces antidepressant-like effects in the forced swim test and in the tail suspension test in mice. Life Sci.,  2007, 81(11), 933-938.
[http://dx.doi.org/10.1016/j.lfs.2007.08.003] [PMID:  17804020] 
[131] 
Yu, H-Y.; Yin, Z.J.; Yang, S.J.; Ma, S.P. Baicalin reverse AMPA receptor expression and neuron apoptosis in chronic unpredictable mild stress rats. Biochem. Biophys. Res. Commun.,  2014, 451(4), 467-472.
[http://dx.doi.org/10.1016/j.bbrc.2014.07.041] [PMID:  25065744] 
[132] 
Neag, M.A.; Mocan, A.; Echeverría, J.; Pop, R.M.; Bocsan, C.I.; Crişan, G.; Buzoianu, A.D. Berberine: Botanical occurrence, traditional uses, extraction methods, and relevance in cardiovascular, metabolic, hepatic, and renal disorders. Front. Pharmacol.,  2018, 9, 557.
[http://dx.doi.org/10.3389/fphar.2018.00557] [PMID:  30186157] 
[133] 
Zhu, X.; Sun, Y.; Zhang, C.; Liu, H. Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays. Mol. Med. Rep.,  2017, 15(5), 3161-3171.
[http://dx.doi.org/10.3892/mmr.2017.6353] [PMID:  28339024] 
[134] 
Fan, J.; Zhang, K.; Jin, Y.; Li, B.; Gao, S.; Zhu, J.; Cui, R. Pharmacological effects of berberine on mood disorders. J. Cell. Mol. Med.,  2019, 23(1), 21-28.
[http://dx.doi.org/10.1111/jcmm.13930] [PMID:  30450823] 
[135] 
Schmidt, H.M.; Kelley, E.E.; Straub, A.C. The impact of xanthine oxidase (XO) on hemolytic diseases. Redox Biol.,  2019, 21, 101072.
[http://dx.doi.org/10.1016/j.redox.2018.101072] [PMID:  30580157] 
[136] 
Lee, B.; Sur, B.; Yeom, M.; Shim, I.; Lee, H.; Hahm, D.H. Effect of berberine on depression- and anxiety-like behaviors and activation of the noradrenergic system induced by development of morphine dependence in rats. Korean J. Physiol. Pharmacol.,  2012, 16(6), 379-386.
[http://dx.doi.org/10.4196/kjpp.2012.16.6.379] [PMID:  23269899] 
[137] 
Fan, J.; Li, B.; Ge, T.; Zhang, Z.; Lv, J.; Zhao, J.; Wang, P.; Liu, W.; Wang, X.; Mlyniec, K.; Cui, R. Berberine produces antidepressant-like effects in ovariectomized mice. Sci. Rep.,  2017, 7(1), 1310.
[http://dx.doi.org/10.1038/s41598-017-01035-5] [PMID:  28465511] 
[138] 
Zhan, Y.; Han, J.; Xia, J.; Wang, X. Berberine Suppresses mice depression behaviors and promotes hippocampal neurons growth through regulating the miR-34b-5p/miR-470-5p/BDNF Axis. Neuropsychiatr. Dis. Treat.,  2021, 17, 613-626.
[http://dx.doi.org/10.2147/NDT.S289444] [PMID:  33654403] 
[139] 
Barati, N.; Momtazi-Borojeni, A.A.; Majeed, M.; Sahebkar, A. Potential therapeutic effects of curcumin in gastric cancer. J. Cell. Physiol.,  2019, 234(3), 2317-2328.
[http://dx.doi.org/10.1002/jcp.27229] [PMID:  30191991] 
[140] 
Ouyang, J. Curcumin protects human umbilical vein endothelial cells against H2O2-induced cell injury. Pain Res. Manag.,  2019, 2019, 3173149.
[http://dx.doi.org/10.1155/2019/3173149] 
[141] 
Zhang, Y.; Zeng, Y. Curcumin reduces inflammation in knee osteoarthritis rats through blocking TLR4/MyD88/NF-κB signal pathway. Drug Dev. Res.,  2019, 80(3), 353-359.
[http://dx.doi.org/10.1002/ddr.21509] [PMID:  30663793] 
[142] 
Golonko, A.; Lewandowska, H.; Świsłocka, R.; Jasińska, U.T.; Priebe, W.; Lewandowski, W. Curcumin as tyrosine kinase inhibitor in cancer treatment. Eur. J. Med. Chem.,  2019, 181, 111512.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.015] [PMID:  31404861] 
[143] 
Pivari, F.; Mingione, A.; Brasacchio, C.; Soldati, L. Curcumin and type 2 diabetes mellitus: Prevention and treatment. Nutrients,  2019, 11(8), 1837.
[http://dx.doi.org/10.3390/nu11081837] [PMID:  31398884] 
[144] 
Gorabi, A.M. Anti-fibrotic effects of curcumin and some of its analogues in the heart. Heart Fail. Rev.,  2020, 25(5), 731-743.
[PMID:  31512150] 
[145] 
Barandeh, B.; Amini Mahabadi, J.; Azadbakht, M.; Gheibi Hayat, S.M.; Amini, A. The protective effects of curcumin on cytotoxic and teratogenic activity of retinoic acid in mouse embryonic liver. J. Cell. Biochem.,  2019, 120(12), 19371-19376.
[http://dx.doi.org/10.1002/jcb.28934] [PMID:  31498479] 
[146] 
Bavarsad, K.; Riahi, M.M.; Saadat, S.; Barreto, G.; Atkin, S.L.; Sahebkar, A. Protective effects of curcumin against ischemia-reperfusion injury in the liver. Pharmacol. Res.,  2019, 141, 53-62.
[http://dx.doi.org/10.1016/j.phrs.2018.12.014] [PMID:  30562571] 
[147] 
Shehzad, A.; Islam, S.U.; Lee, Y.S. Curcumin and inflammatory brain diseases.  In:Curcumin for Neurological and Psychiatric Disorders; Elsevier, 2019, pp. 437-458.
[http://dx.doi.org/10.1016/B978-0-12-815461-8.00024-4] 
[148] 
Okereke, O.I.; Cook, N.R.; Albert, C.M.; Van Denburgh, M.; Buring, J.E.; Manson, J.E. Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women. Br. J. Psychiatry,  2015, 206(4), 324-331.
[http://dx.doi.org/10.1192/bjp.bp.114.148361] [PMID:  25573400] 
[149] 
Kulkarni, S.K.; Bhutani, M.K.; Bishnoi, M. Antidepressant activity of curcumin: Involvement of serotonin and dopamine system. Psychopharmacology (Berl.),  2008, 201(3), 435-442.
[http://dx.doi.org/10.1007/s00213-008-1300-y] [PMID:  18766332] 
[150] 
Ng, Q.X.; Koh, S.S.H.; Chan, H.W.; Ho, C.Y.X. Clinical use of curcumin in depression: A meta-analysis. J. Am. Med. Dir. Assoc.,  2017, 18(6), 503-508.
[http://dx.doi.org/10.1016/j.jamda.2016.12.071] [PMID:  28236605] 
[151] 
Bhutani, M.K.; Bishnoi, M.; Kulkarni, S.K. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol. Biochem. Behav.,  2009, 92(1), 39-43.
[http://dx.doi.org/10.1016/j.pbb.2008.10.007] [PMID:  19000708] 
[152] 
Nazemi, H.; Mirzaei, M.; Jafari, E. Antidepressant activity of curcumin by monoamine oxidase–A inhibition. Adv. J. Chem.-Section B,  2019, 1(1), 3-9.
[http://dx.doi.org/10.33945/SAMI/AJCB.2019.1.2] 
[153] 
Andrade, C. A critical examination of studies on curcumin for depression. J. Clin. Psychiatry,  2014, 75(10)
[http://dx.doi.org/10.4088/JCP.14f09489] 
[154] 
Baek, S.C. Inhibition of monoamine oxidase A and B by demethoxycurcumin and bisdemethoxycurcumin. J. Appl. Biol. Chem.,  2018, 61(2), 187-190.
[http://dx.doi.org/10.3839/jabc.2018.027] 
[155] 
Fusar-Poli, L.; Vozza, L.; Gabbiadini, A.; Vanella, A.; Concas, I.; Tinacci, S.; Petralia, A.; Signorelli, M.S.; Aguglia, E. Curcumin for depression: A meta-analysis. Crit. Rev. Food Sci. Nutr.,  2020, 60(15), 2643-2653.
[http://dx.doi.org/10.1080/10408398.2019.1653260] [PMID:  31423805] 
[156] 
Rosa, P.B.; Ribeiro, C.M.; Bettio, L.E.; Colla, A.; Lieberknecht, V.; Moretti, M.; Rodrigues, A.L. Folic acid prevents depressive-like behavior induced by chronic corticosterone treatment in mice. Pharmacol. Biochem. Behav.,  2014, 127, 1-6.
[http://dx.doi.org/10.1016/j.pbb.2014.10.003] [PMID:  25316305] 
[157] 
Yan, J.; Liu, Y.; Cao, L.; Zheng, Y.; Li, W.; Huang, G. Association between duration of folic acid supplementation during pregnancy and risk of postpartum depression. Nutrients,  2017, 9(11), 1206.
[http://dx.doi.org/10.3390/nu9111206] [PMID:  29099069] 
[158] 
Zhou, Y.; Cong, Y.; Liu, H. Folic acid ameliorates depression-like behaviour in a rat model of chronic unpredictable mild stress. BMC Neurosci.,  2020, 21(1), 1-8.
[http://dx.doi.org/10.1186/s12868-020-0551-3] [PMID:  31941442] 
[159] 
Bender, A.; Hagan, K.E.; Kingston, N. The association of folate and depression: A meta-analysis. J. Psychiatr. Res.,  2017, 95, 9-18.
[http://dx.doi.org/10.1016/j.jpsychires.2017.07.019] [PMID:  28759846] 
[160] 
De Long, N.E.; Hyslop, J.R.; Raha, S.; Hardy, D.B.; Holloway, A.C. Fluoxetine-induced pancreatic beta cell dysfunction: New insight into the benefits of folic acid in the treatment of depression. J. Affect. Disord.,  2014, 166, 6-13.
[http://dx.doi.org/10.1016/j.jad.2014.04.063] [PMID:  25012404] 
[161] 
Noori, T.; Dehpour, A.R.; Sureda, A.; Sobarzo-Sanchez, E.; Shirooie, S. Role of natural products for the treatment of Alzheimer’s disease. Eur. J. Pharmacol.,  2021, 898, 173974.
[http://dx.doi.org/10.1016/j.ejphar.2021.173974] [PMID:  33652057] 
[162] 
Tian, J-S.; Cui, Y.L.; Hu, L.M.; Gao, S.; Chi, W.; Dong, T.J.; Liu, L.P. Antidepressant-like effect of genipin in mice. Neurosci. Lett.,  2010, 479(3), 236-239.
[http://dx.doi.org/10.1016/j.neulet.2010.05.069] [PMID:  20561935] 
[163] 
Cai, L.; Li, R.; Tang, W.J.; Meng, G.; Hu, X.Y.; Wu, T.N. Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis. Eur. Neuropsychopharmacol.,  2015, 25(8), 1332-1341.
[http://dx.doi.org/10.1016/j.euroneuro.2015.04.009] [PMID:  25914157] 
[164] 
Wang, J.; Duan, P.; Cui, Y.; Li, Q.; Shi, Y. Geniposide alleviates depression-like behavior via enhancing BDNF expression in hippocampus of streptozotocin-evoked mice. Metab. Brain Dis.,  2016, 31(5), 1113-1122.
[http://dx.doi.org/10.1007/s11011-016-9856-4] [PMID:  27311609] 
[165] 
Koo, H-J.; Lim, K.H.; Jung, H.J.; Park, E.H. Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. J. Ethnopharmacol.,  2006, 103(3), 496-500.
[http://dx.doi.org/10.1016/j.jep.2005.08.011] [PMID:  16169698] 
[166] 
Park, E.H.; Joo, M.H.; Kim, S.H.; Lim, C.J. Antiangiogenic activity of Gardenia jasminoides fruit. Phytother. Res.,  2003, 17(8), 961-962.
[http://dx.doi.org/10.1002/ptr.1259] [PMID:  13680835] 
[167] 
Koriyama, Y.; Chiba, K.; Yamazaki, M.; Suzuki, H.; Muramoto, K.; Kato, S. Long-acting genipin derivative protects retinal ganglion cells from oxidative stress models in vitro and in vivo through the Nrf2/antioxidant response element signaling pathway. J. Neurochem.,  2010, 115(1), 79-91.
[http://dx.doi.org/10.1111/j.1471-4159.2010.06903.x] [PMID:  20681953] 
[168] 
Tan, H-Y.; Wang, N.; Tsao, S.W.; Che, C.M.; Yuen, M.F.; Feng, Y. IRE1α inhibition by natural compound genipin on tumour associated macrophages reduces growth of hepatocellular carcinoma. Oncotarget,  2016, 7(28), 43792-43804.
[http://dx.doi.org/10.18632/oncotarget.9696] [PMID:  27270308] 
[169] 
Li, Y.; Li, L.; Hölscher, C. Therapeutic potential of genipin in central neurodegenerative diseases. CNS Drugs,  2016, 30(10), 889-897.
[http://dx.doi.org/10.1007/s40263-016-0369-9] [PMID:  27395402] 
[170] 
Wang, Q-S.; Tian, J.S.; Cui, Y.L.; Gao, S. Genipin is active via modulating monoaminergic transmission and levels of brain-derived neurotrophic factor (BDNF) in rat model of depression. Neuroscience,  2014, 275, 365-373.
[http://dx.doi.org/10.1016/j.neuroscience.2014.06.032] [PMID:  24972301] 
[171] 
Kageyama, A.; Sakakibara, H.; Zhou, W.; Yoshioka, M.; Ohsumi, M.; Shimoi, K.; Yokogoshi, H. Genistein regulated serotonergic activity in the hippocampus of ovariectomized rats under forced swimming stress. Biosci. Biotechnol. Biochem.,  2010, 74(10), 2005-2010.
[http://dx.doi.org/10.1271/bbb.100238] [PMID:  20944428] 
[172] 
Marini, H.; Bitto, A.; Altavilla, D.; Burnett, B.P.; Polito, F.; Di Stefano, V.; Minutoli, L.; Atteritano, M.; Levy, R.M.; Frisina, N.; Mazzaferro, S.; Frisina, A.; D’Anna, R.; Cancellieri, F.; Cannata, M.L.; Corrado, F.; Lubrano, C.; Marini, R.; Adamo, E.B.; Squadrito, F. Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study. Nutr. Metab. Cardiovasc. Dis.,  2010, 20(5), 332-340.
[http://dx.doi.org/10.1016/j.numecd.2009.04.012] [PMID:  19631515] 
[173] 
Atteritano, M.; Mazzaferro, S.; Bitto, A.; Cannata, M.L.; D’Anna, R.; Squadrito, F.; Macrì, I.; Frisina, A.; Frisina, N.; Bagnato, G. Genistein effects on quality of life and depression symptoms in osteopenic postmenopausal women: A 2-year randomized, double-blind, controlled study. Osteoporos. Int.,  2014, 25(3), 1123-1129.
[http://dx.doi.org/10.1007/s00198-013-2512-5] [PMID:  24114397] 
[174] 
Thangavel, P.; Puga-Olguín, A.; Rodríguez-Landa, J.F.; Zepeda, R.C. Genistein as potential therapeutic candidate for menopausal symptoms and other related diseases. Molecules,  2019, 24(21), 3892.
[http://dx.doi.org/10.3390/molecules24213892] [PMID:  31671813] 
[175] 
Baffa, A.; Hohoff, C.; Baune, B.T.; Müller-Tidow, C.; Tidow, N.; Freitag, C.; Zwanzger, P.; Deckert, J.; Arolt, V.; Domschke, K. Norepinephrine and serotonin transporter genes: Impact on treatment response in depression. Neuropsychobiology,  2010, 62(2), 121-131.
[http://dx.doi.org/10.1159/000317285] [PMID:  20588071] 
[176] 
Baudry, A.; Mouillet-Richard, S.; Launay, J.M.; Kellermann, O. New views on antidepressant action. Curr. Opin. Neurobiol.,  2011, 21(6), 858-865.
[http://dx.doi.org/10.1016/j.conb.2011.03.005] [PMID:  21530233] 
[177] 
Baudry, A.; Mouillet-Richard, S.; Schneider, B.; Launay, J.M.; Kellermann, O. miR-16 targets the serotonin transporter: A new facet for adaptive responses to antidepressants. Science,  2010, 329(5998), 1537-1541.
[http://dx.doi.org/10.1126/science.1193692] [PMID:  20847275] 
[178] 
Hu, P.; Ma, L.; Wang, Y.G.; Ye, F.; Wang, C.; Zhou, W.H.; Zhao, X. Genistein, a dietary soy isoflavone, exerts antidepressant-like effects in mice: Involvement of serotonergic system. Neurochem. Int.,  2017, 108, 426-435.
[http://dx.doi.org/10.1016/j.neuint.2017.06.002] [PMID:  28606822] 
[179] 
Gupta, G. Pharmacological evaluation of antidepressant-like effect of genistein and its combination with amitriptyline: An acute and chronic study. Adv. Pharmacol. Sci.,  2015, 2015, 164943.
[http://dx.doi.org/10.1155/2015/164943] 
[180] 
Zarmouh, N.O. Evaluation of the isoflavone genistein as reversible human monoamine oxidase-A and-B inhibitor. Evid. Based Complement. Alternat. Med.,  2016, 2016, 1423052.
[http://dx.doi.org/10.1155/2016/1423052] 
[181] 
Ishisaka, M.; Kakefuda, K.; Yamauchi, M.; Tsuruma, K.; Shimazawa, M.; Tsuruta, A.; Hara, H. Luteolin shows an antidepressant-like effect via suppressing endoplasmic reticulum stress. Biol. Pharm. Bull.,  2011, 34(9), 1481-1486.
[http://dx.doi.org/10.1248/bpb.34.1481] [PMID:  21881237] 
[182] 
Zhu, L-H.; Bi, W.; Qi, R.B.; Wang, H.D.; Lu, D.X. Luteolin inhibits microglial inflammation and improves neuron survival against inflammation. Int. J. Neurosci.,  2011, 121(6), 329-336.
[http://dx.doi.org/10.3109/00207454.2011.569040] [PMID:  21631167] 
[183] 
Gupta, G.; Tiwari, J.; Dahiya, R.; Kumar Sharma, R.; Mishra, A.; Dua, K. Recent updates on neuropharmacological effects of luteolin. EXCLI J.,  2018, 17, 211-214.
[PMID:  29743859] 
[184] 
Lee, J.K.; Kim, S.Y.; Kim, Y.S.; Lee, W.H.; Hwang, D.H.; Lee, J.Y. Suppression of the TRIF-dependent signaling pathway of Toll-like receptors by luteolin. Biochem. Pharmacol.,  2009, 77(8), 1391-1400.
[http://dx.doi.org/10.1016/j.bcp.2009.01.009] [PMID:  19426678] 
[185] 
Weng, Z. The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells. J. Allergy Clin. Immunol.,  2015, 135(4), 1044-1052.
[http://dx.doi.org/10.1016/j.jaci.2014.10.032] 
[186] 
Lin, C-W.; Wu, M.J.; Liu, I.Y.; Su, J.D.; Yen, J.H. Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK-dependent induction of Nrf2-driven HO-1 expression. J. Agric. Food Chem.,  2010, 58(7), 4477-4486.
[http://dx.doi.org/10.1021/jf904061x] [PMID:  20302373] 
[187] 
Patil, S.P.; Jain, P.D.; Sancheti, J.S.; Ghumatkar, P.J.; Tambe, R.; Sathaye, S. Neuroprotective and neurotrophic effects of Apigenin and Luteolin in MPTP induced parkinsonism in mice. Neuropharmacology,  2014, 86, 192-202.
[http://dx.doi.org/10.1016/j.neuropharm.2014.07.012] [PMID:  25087727] 
[188] 
Kritas, S.K.; Saggini, A.; Varvara, G.; Murmura, G.; Caraffa, A.; Antinolfi, P.; Toniato, E.; Pantalone, A.; Neri, G.; Frydas, S.; Rosati, M.; Tei, M.; Speziali, A.; Saggini, R.; Pandolfi, F.; Cerulli, G.; Theoharides, T.C.; Conti, P. Luteolin inhibits mast cell-mediated allergic inflammation. J. Biol. Regul. Homeost. Agents,  2013, 27(4), 955-959.
[PMID:  24382176] 
[189] 
Mokhtari, V.; Afsharian, P.; Shahhoseini, M.; Kalantar, S.M.; Moini, A. A review on various uses of N-acetyl cysteine. Cell J.,  2017, 19(1), 11-17.
[PMID:  28367412] 
[190] 
Minarini, A.; Ferrari, S.; Galletti, M.; Giambalvo, N.; Perrone, D.; Rioli, G.; Galeazzi, G.M. N-acetylcysteine in the treatment of psychiatric disorders: Current status and future prospects. Expert Opin. Drug Metab. Toxicol.,  2017, 13(3), 279-292.
[http://dx.doi.org/10.1080/17425255.2017.1251580] [PMID:  27766914] 
[191] 
Berk, M.; Dean, O.; Cotton, S.M.; Gama, C.S.; Kapczinski, F.; Fernandes, B.S.; Kohlmann, K.; Jeavons, S.; Hewitt, K.; Allwang, C.; Cobb, H.; Bush, A.I.; Schapkaitz, I.; Dodd, S.; Malhi, G.S. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: An open label trial. J. Affect. Disord.,  2011, 135(1-3), 389-394.
[http://dx.doi.org/10.1016/j.jad.2011.06.005] [PMID:  21719110] 
[192] 
Porcu, M.; Urbano, M.R.; Verri, W.A., Jr; Barbosa, D.S.; Baracat, M.; Vargas, H.O.; Machado, R.C.B.R.; Pescim, R.R.; Nunes, S.O.V. Effects of adjunctive N-acetylcysteine on depressive symptoms: Modulation by baseline high-sensitivity C-reactive protein. Psychiatry Res.,  2018, 263, 268-274.
[http://dx.doi.org/10.1016/j.psychres.2018.02.056] [PMID:  29605103] 
[193] 
Ellegaard, P.K.; Licht, R.W.; Poulsen, H.E.; Nielsen, R.E.; Berk, M.; Dean, O.M.; Mohebbi, M.; Nielsen, C.T. Add-on treatment with N-acetylcysteine for bipolar depression: A 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol). Int. J. Bipolar Disord.,  2018, 6(1), 11.
[http://dx.doi.org/10.1186/s40345-018-0117-9] [PMID:  29619634] 
[194] 
Wright, D.J.; Gray, L.J.; Finkelstein, D.I.; Crouch, P.J.; Pow, D.; Pang, T.Y.; Li, S.; Smith, Z.M.; Francis, P.S.; Renoir, T.; Hannan, A.J. N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington’s disease. Hum. Mol. Genet.,  2016, 25(14), 2923-2933.
[http://dx.doi.org/10.1093/hmg/ddw144] [PMID:  27179791] 
[195] 
Réus, G.Z.; Dos Santos, M.A.; Abelaira, H.M.; Titus, S.E.; Carlessi, A.S.; Matias, B.I.; Bruchchen, L.; Florentino, D.; Vieira, A.; Petronilho, F.; Ceretta, L.B.; Zugno, A.I.; Quevedo, J. Antioxidant treatment ameliorates experimental diabetes-induced depressive-like behaviour and reduces oxidative stress in brain and pancreas. Diabetes Metab. Res. Rev.,  2016, 32(3), 278-288.
[http://dx.doi.org/10.1002/dmrr.2732] [PMID:  26432993] 
[196] 
Willner, P. The chronic mild stress (CMS) model of depression: History, evaluation and usage. Neurobiol. Stress,  2016, 6, 78-93.
[http://dx.doi.org/10.1016/j.ynstr.2016.08.002] [PMID:  28229111] 
[197] 
Lebourgeois, S.; González-Marín, M.C.; Jeanblanc, J.; Naassila, M.; Vilpoux, C. Effect of N-acetylcysteine on motivation, seeking and relapse to ethanol self-administration. Addict. Biol.,  2018, 23(2), 643-652.
[http://dx.doi.org/10.1111/adb.12521] [PMID:  28557352] 
[198] 
Soliman, N.A.; Zineldeen, D.H.; Katary, M.A.; Ali, D.A. N-acetylcysteine a possible protector against indomethacin-induced peptic ulcer: Crosstalk between antioxidant, anti-inflammatory, and antiapoptotic mechanisms. Can. J. Physiol. Pharmacol.,  2017, 95(4), 396-403.
[http://dx.doi.org/10.1139/cjpp-2016-0442] [PMID:  28092180] 
[199] 
Ge, J-F.; Gao, W.C.; Cheng, W.M.; Lu, W.L.; Tang, J.; Peng, L.; Li, N.; Chen, F.H. Orcinol glucoside produces antidepressant effects by blocking the behavioural and neuronal deficits caused by chronic stress. Eur. Neuropsychopharmacol.,  2014, 24(1), 172-180.
[http://dx.doi.org/10.1016/j.euroneuro.2013.05.007] [PMID:  23838013] 
[200] 
Gupta, G.L.; Fernandes, J. Protective effect of Convolvulus pluricaulis against neuroinflammation associated depressive behavior induced by chronic unpredictable mild stress in rat. Biomed. Pharmacother.,  2019, 109, 1698-1708.
[http://dx.doi.org/10.1016/j.biopha.2018.11.046] [PMID:  30551424] 
[201] 
Smaga, I.; Pomierny, B.; Krzyżanowska, W.; Pomierny-Chamioło, L.; Miszkiel, J.; Niedzielska, E.; Ogórka, A.; Filip, M. N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: Behavioral and biochemical analyses in rats. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2012, 39(2), 280-287.
[http://dx.doi.org/10.1016/j.pnpbp.2012.06.018] [PMID:  22820675] 
[202] 
Arent, C.O.; Réus, G.Z.; Abelaira, H.M.; Ribeiro, K.F.; Steckert, A.V.; Mina, F.; Dal-Pizzol, F.; Quevedo, J. Synergist effects of n-acetylcysteine and deferoxamine treatment on behavioral and oxidative parameters induced by chronic mild stress in rats. Neurochem. Int.,  2012, 61(7), 1072-1080.
[http://dx.doi.org/10.1016/j.neuint.2012.07.024] [PMID:  22898295] 
[203] 
Zheng, W.; Zhang, Q.E.; Cai, D.B.; Yang, X.H.; Qiu, Y.; Ungvari, G.S.; Ng, C.H.; Berk, M.; Ning, Y.P.; Xiang, Y.T. N-acetylcysteine for major mental disorders: A systematic review and meta-analysis of randomized controlled trials. Acta Psychiatr. Scand.,  2018, 137(5), 391-400.
[http://dx.doi.org/10.1111/acps.12862] [PMID:  29457216] 
[204] 
Fernandes, J.; Gupta, G.L. N-acetylcysteine attenuates neuroinflammation associated depressive behavior induced by chronic unpredictable mild stress in rat. Behav. Brain Res.,  2019, 364, 356-365.
[http://dx.doi.org/10.1016/j.bbr.2019.02.025] [PMID:  30772427] 
[205] 
Yi, L-T.; Li, J.; Li, H.C.; Su, D.X.; Quan, X.B.; He, X.C.; Wang, X.H. Antidepressant-like behavioral, neurochemical and neuroendocrine effects of naringenin in the mouse repeated tail suspension test. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2012, 39(1), 175-181.
[http://dx.doi.org/10.1016/j.pnpbp.2012.06.009] [PMID:  22709719] 
[206] 
Yi, L-T.; Liu, B.B.; Li, J.; Luo, L.; Liu, Q.; Geng, D.; Tang, Y.; Xia, Y.; Wu, D. BDNF signaling is necessary for the antidepressant-like effect of naringenin. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2014, 48, 135-141.
[http://dx.doi.org/10.1016/j.pnpbp.2013.10.002] [PMID:  24121063] 
[207] 
Yi, L-T.; Li, C.F.; Zhan, X.; Cui, C.C.; Xiao, F.; Zhou, L.P.; Xie, Y. Involvement of monoaminergic system in the antidepressant-like effect of the flavonoid naringenin in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2010, 34(7), 1223-1228.
[http://dx.doi.org/10.1016/j.pnpbp.2010.06.024] [PMID:  20603175] 
[208] 
Bansal, Y.; Singh, R.; Saroj, P.; Sodhi, R.K.; Kuhad, A. Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression. Toxicol. Appl. Pharmacol.,  2018, 355, 257-268.
[http://dx.doi.org/10.1016/j.taap.2018.07.010] [PMID:  30017640] 
[209] 
Mao, Q-Q.; Xian, Y.F.; Ip, S.P.; Che, C.T. Involvement of serotonergic system in the antidepressant-like effect of piperine. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(4), 1144-1147.
[http://dx.doi.org/10.1016/j.pnpbp.2011.03.017] [PMID:  21477634] 
[210] 
Mao, Q-Q.; Huang, Z.; Zhong, X.M.; Xian, Y.F.; Ip, S.P. Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice. Neurochem. Int.,  2014, 74, 36-41.
[http://dx.doi.org/10.1016/j.neuint.2014.04.017] [PMID:  24816193] 
[211] 
Lee, S.A.; Hong, S.S.; Han, X.H.; Hwang, J.S.; Oh, G.J.; Lee, K.S.; Lee, M.K.; Hwang, B.Y.; Ro, J.S. Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant-like activity. Chem. Pharm. Bull. (Tokyo),  2005, 53(7), 832-835.
[http://dx.doi.org/10.1248/cpb.53.832] [PMID:  15997146] 
[212] 
Li, S.; Wang, C.; Li, W.; Koike, K.; Nikaido, T.; Wang, M.W. Antidepressant-like effects of piperine and its derivative, antiepilepsirine. J. Asian Nat. Prod. Res.,  2007, 9(3-5), 421-430.
[http://dx.doi.org/10.1080/10286020500384302] [PMID:  17701559] 
[213] 
Mao, Q-Q.; Huang, Z.; Ip, S.P.; Xian, Y.F.; Che, C.T. Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of piperine in the forced swim test. Neurosci. Lett.,  2011, 504(2), 181-184.
[http://dx.doi.org/10.1016/j.neulet.2011.09.038] [PMID:  21964383] 
[214] 
Mao, Q-Q.; Huang, Z.; Ip, S.P.; Xian, Y.F.; Che, C.T. Protective effects of piperine against corticosterone-induced neurotoxicity in PC12 cells. Cell. Mol. Neurobiol.,  2012, 32(4), 531-537.
[http://dx.doi.org/10.1007/s10571-011-9786-y] [PMID:  22205277] 
[215] 
Mao, Q-Q.; Huang, Z.; Ip, S.P.; Xian, Y.F.; Che, C.T. Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats. Behav. Brain Res.,  2012, 227(1), 305-309.
[http://dx.doi.org/10.1016/j.bbr.2011.11.016] [PMID:  22119711] 
[216] 
Vaibhav, K.; Shrivastava, P.; Javed, H.; Khan, A.; Ahmed, M.E.; Tabassum, R.; Khan, M.M.; Khuwaja, G.; Islam, F.; Siddiqui, M.S.; Safhi, M.M.; Islam, F. Piperine suppresses cerebral ischemia-reperfusion-induced inflammation through the repression of COX-2, NOS-2, and NF-κB in middle cerebral artery occlusion rat model. Mol. Cell. Biochem.,  2012, 367(1-2), 73-84.
[http://dx.doi.org/10.1007/s11010-012-1321-z] [PMID:  22669728] 
[217] 
Li, S.; Wang, C.; Wang, M.; Li, W.; Matsumoto, K.; Tang, Y. Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Life Sci.,  2007, 80(15), 1373-1381.
[http://dx.doi.org/10.1016/j.lfs.2006.12.027] [PMID:  17289085] 
[218] 
Rinwa, P.; Kumar, A.; Garg, S. Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression. PLoS One,  2013, 8(4), e61052.
[http://dx.doi.org/10.1371/journal.pone.0061052] [PMID:  23613781] 
[219] 
Shinozaki, T.; Yamada, T.; Nonaka, T.; Yamamoto, T. Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats. J. Anesth.,  2015, 29(3), 386-395.
[http://dx.doi.org/10.1007/s00540-014-1953-0] [PMID:  25424590] 
[220] 
Bhutada, P.; Mundhada, Y.; Bansod, K.; Bhutada, C.; Tawari, S.; Dixit, P.; Mundhada, D. Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats. Neurobiol. Learn. Mem.,  2010, 94(3), 293-302.
[http://dx.doi.org/10.1016/j.nlm.2010.06.008] [PMID:  20620214] 
[221] 
Samad, N.; Saleem, A.; Yasmin, F.; Shehzad, M.A. Quercetin protects against stress-induced anxiety- and depression-like behavior and improves memory in male mice. Physiol. Res.,  2018, 67(5), 795-808.
[http://dx.doi.org/10.33549/physiolres.933776] [PMID:  30044120] 
[222] 
Kawabata, K.; Kawai, Y.; Terao, J. Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats. J. Nutr. Biochem.,  2010, 21(5), 374-380.
[http://dx.doi.org/10.1016/j.jnutbio.2009.01.008] [PMID:  19423323] 
[223] 
Halder, S.; Kar, R.; Mehta, A.K.; Bhattacharya, S.K.; Mediratta, P.K.; Banerjee, B.D. Quercetin modulates the effects of chromium exposure on learning, memory and antioxidant enzyme activity in F 1 generation mice. Biol. Trace Elem. Res.,  2016, 171(2), 391-398.
[http://dx.doi.org/10.1007/s12011-015-0544-8] [PMID:  26521059] 
[224] 
Merzoug, S.; Toumi, M.L.; Tahraoui, A. Quercetin mitigates Adriamycin-induced anxiety- and depression-like behaviors, immune dysfunction, and brain oxidative stress in rats. Naunyn Schmiedebergs Arch. Pharmacol.,  2014, 387(10), 921-933.
[http://dx.doi.org/10.1007/s00210-014-1008-y] [PMID:  24947870] 
[225] 
Lee, B. Protective effects of quercetin on anxiety-like symptoms and Neuroinflammation induced by lipopolysaccharide in rats. Evid. Based Complement. Alternat. Med.,  2020, 2020, 4892415.
[http://dx.doi.org/10.1155/2020/4892415] 
[226] 
Fang, K.; Li, H.R.; Chen, X.X.; Gao, X.R.; Huang, L.L.; Du, A.Q.; Jiang, C.; Li, H.; Ge, J.F. Quercetin alleviates LPS-induced depression-like behavior in rats via regulating BDNF-related imbalance of Copine 6 and TREM1/2 in the hippocampus and PFC. Front. Pharmacol.,  2020, 10, 1544.
[http://dx.doi.org/10.3389/fphar.2019.01544] [PMID:  32009956] 
[227] 
Legeay, S.; Rodier, M.; Fillon, L.; Faure, S.; Clere, N. Epigallocatechin gallate: A review of its beneficial properties to prevent metabolic syndrome. Nutrients,  2015, 7(7), 5443-5468.
[http://dx.doi.org/10.3390/nu7075230] [PMID:  26198245] 
[228] 
Peairs, A.; Dai, R.; Gan, L.; Shimp, S.; Rylander, M.N.; Li, L.; Reilly, C.M. Epigallocatechin-3-gallate (EGCG) attenuates inflammation in MRL/lpr mouse mesangial cells. Cell. Mol. Immunol.,  2010, 7(2), 123-132.
[http://dx.doi.org/10.1038/cmi.2010.1] [PMID:  20140007] 
[229] 
El-Missiry, M.A.; Othman, A.I.; El-Sawy, M.R.; Lebede, M.F. Neuroprotective effect of epigallocatechin-3-gallate (EGCG) on radiation-induced damage and apoptosis in the rat hippocampus. Int. J. Radiat. Biol.,  2018, 94(9), 798-808.
[http://dx.doi.org/10.1080/09553002.2018.1492755] [PMID:  29939076] 
[230] 
Wang, J. Antidepressant effect of EGCG through the inhibition of hippocampal neuroinflammation in chronic unpredictable mild stress-induced depression rat model. J. Funct. Foods,  2020, 73, 104106.
[http://dx.doi.org/10.1016/j.jff.2020.104106] 
[231] 
Lee, B.; Shim, I.; Lee, H.; Hahm, D.H. Effects of epigallocatechin gallate on behavioral and cognitive impairments, hypothalamic–pituitary–adrenal Axis dysfunction, and alternations in hippocampal BDNF expression under single prolonged stress. J. Med. Food,  2018, 21(10), 979-989.
[http://dx.doi.org/10.1089/jmf.2017.4161] [PMID:  30273101] 
[232] 
Gambini, J. Properties of resveratrol: In vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxid. Med. Cell. Longev.,  2015, 2015, 837042.
[233] 
Hurley, L.L.; Akinfiresoye, L.; Kalejaiye, O.; Tizabi, Y. Antidepressant effects of resveratrol in an animal model of depression. Behav. Brain Res.,  2014, 268, 1-7.
[http://dx.doi.org/10.1016/j.bbr.2014.03.052] [PMID:  24717328] 
[234] 
Xu, Y.; Wang, Z.; You, W.; Zhang, X.; Li, S.; Barish, P.A.; Vernon, M.M.; Du, X.; Li, G.; Pan, J.; Ogle, W.O. Antidepressant-like effect of trans-resveratrol: Involvement of serotonin and noradrenaline system. Eur. Neuropsychopharmacol.,  2010, 20(6), 405-413.
[http://dx.doi.org/10.1016/j.euroneuro.2010.02.013] [PMID:  20353885] 
[235] 
Moore, A.; Beidler, J.; Hong, M.Y. Resveratrol and depression in animal models: A systematic review of the biological mechanisms. Molecules,  2018, 23(9), 2197.
[http://dx.doi.org/10.3390/molecules23092197] [PMID:  30200269] 
[236] 
Albani, D.; Polito, L.; Signorini, A.; Forloni, G. Neuroprotective properties of resveratrol in different neurodegenerative disorders. Biofactors,  2010, 36(5), 370-376.
[http://dx.doi.org/10.1002/biof.118] [PMID:  20848560] 
[237] 
Bhandari, R.; Kuhad, A. Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders. Neurochem. Int.,  2017, 103, 8-23.
[http://dx.doi.org/10.1016/j.neuint.2016.12.012] [PMID:  28025035] 
[238] 
Gocmez, S.S.; Gacar, N.; Utkan, T.; Gacar, G.; Scarpace, P.J.; Tumer, N. Protective effects of resveratrol on aging-induced cognitive impairment in rats. Neurobiol. Learn. Mem.,  2016, 131, 131-136.
[http://dx.doi.org/10.1016/j.nlm.2016.03.022] [PMID:  27040098] 
[239] 
Gu, Z.; Chu, L.; Han, Y. Therapeutic effect of resveratrol on mice with depression. Exp. Ther. Med.,  2019, 17(4), 3061-3064.
[http://dx.doi.org/10.3892/etm.2019.7311] [PMID:  30936978] 
[240] 
Ali, S.H.; Madhana, R.M. K v, A.; Kasala, E.R.; Bodduluru, L.N.; Pitta, S.; Mahareddy, J.R.; Lahkar, M. Resveratrol ameliorates depressive-like behavior in repeated corticosterone-induced depression in mice. Steroids,  2015, 101, 37-42.
[http://dx.doi.org/10.1016/j.steroids.2015.05.010] [PMID:  26048446] 
[241] 
Chen, W-J.; Du, J.K.; Hu, X.; Yu, Q.; Li, D.X.; Wang, C.N.; Zhu, X.Y.; Liu, Y.J. Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior. Physiol. Behav.,  2017, 182, 54-61.
[http://dx.doi.org/10.1016/j.physbeh.2017.09.024] [PMID:  28964807] 
[242] 
Liu, L.; Zhang, Q.; Cai, Y.; Sun, D.; He, X.; Wang, L.; Yu, D.; Li, X.; Xiong, X.; Xu, H.; Yang, Q.; Fan, X. Resveratrol counteracts lipopolysaccharide-induced depressive-like behaviors via enhanced hippocampal neurogenesis. Oncotarget,  2016, 7(35), 56045-56059.
[http://dx.doi.org/10.18632/oncotarget.11178] [PMID:  27517628] 
[243] 
Jin, X.; Liu, P.; Yang, F.; Zhang, Y.H.; Miao, D. Rosmarinic acid ameliorates depressive-like behaviors in a rat model of CUS and Up-regulates BDNF levels in the hippocampus and hippocampal-derived astrocytes. Neurochem. Res.,  2013, 38(9), 1828-1837.
[http://dx.doi.org/10.1007/s11064-013-1088-y] [PMID:  23756732] 
[244] 
Makhathini, K.B.; Mabandla, M.V.; Daniels, W.M.U. Rosmarinic acid reverses the deleterious effects of repetitive stress and tat protein. Behav. Brain Res.,  2018, 353, 203-209.
[http://dx.doi.org/10.1016/j.bbr.2018.07.010] [PMID:  30029998] 
[245] 
Nadeem, M. Therapeutic potential of rosmarinic acid: A comprehensive review. Appl. Sci. (Basel),  2019, 9(15), 3139.
[http://dx.doi.org/10.3390/app9153139] 
[246] 
Sasaki, K.; El Omri, A.; Kondo, S.; Han, J.; Isoda, H. Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation. Behav. Brain Res.,  2013, 238, 86-94.
[http://dx.doi.org/10.1016/j.bbr.2012.10.010] [PMID:  23085339] 
[247] 
Ghasemzadeh, R.M.; Hosseinzadeh, H. Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders. Iran. J. Basic Med. Sci.,  2020, 23(9), 1100-1112.
[PMID:  32963731] 
[248] 
Kondo, S. Antidepressant-like effects of rosmarinic acid through mitogen-activated protein kinase phosphatase-1 and brain-derived neurotrophic factor modulation. J. Funct. Foods,  2015, 14, 758-766.
[http://dx.doi.org/10.1016/j.jff.2015.03.001] 
[249] 
Nie, H.; Peng, Z.; Lao, N.; Wang, H.; Chen, Y.; Fang, Z.; Hou, W.; Gao, F.; Li, X.; Xiong, L.; Tan, Q. Rosmarinic acid ameliorates PTSD-like symptoms in a rat model and promotes cell proliferation in the hippocampus. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2014, 51, 16-22.
[http://dx.doi.org/10.1016/j.pnpbp.2014.01.002] [PMID:  24418162] 
[250] 
Hwang, E-S.; Kim, H.B.; Choi, G.Y.; Lee, S.; Lee, S.O.; Kim, S.; Park, J.H. Acute rosmarinic acid treatment enhances long-term potentiation, BDNF and GluR-2 protein expression, and cell survival rate against scopolamine challenge in rat organotypic hippocampal slice cultures. Biochem. Biophys. Res. Commun.,  2016, 475(1), 44-50.
[http://dx.doi.org/10.1016/j.bbrc.2016.04.153] [PMID:  27163641] 
[251] 
Maes, M.; Leonard, B.; Fernandez, A.; Kubera, M.; Nowak, G.; Veerhuis, R.; Gardner, A.; Ruckoanich, P.; Geffard, M.; Altamura, C.; Galecki, P.; Berk, M. (Neuro)inflammation and neuroprogression as new pathways and drug targets in depression: From antioxidants to kinase inhibitors. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2011, 35(3), 659-663.
[http://dx.doi.org/10.1016/j.pnpbp.2011.02.019] [PMID:  21376099] 
[252] 
Marx, W.; Lane, M.; Rocks, T.; Ruusunen, A.; Loughman, A.; Lopresti, A.; Marshall, S.; Berk, M.; Jacka, F.; Dean, O.M. Effect of saffron supplementation on symptoms of depression and anxiety: A systematic review and meta-analysis. Nutr. Rev.,  2019, 77(8), 557-571.
[http://dx.doi.org/10.1093/nutrit/nuz023] [PMID:  31135916] 
[253] 
Hosseinzadeh, H.; Ziaei, T. Effects of Crocus sativus stigma extract and its constituents, crocin and safranal, on intact memory and scopolamine-induced learning deficits in rats performing the Morris water maze task. J. Med. Plants,  2006, 5, 40-50.
[254] 
Shafiee, M.; Arekhi, S.; Omranzadeh, A.; Sahebkar, A. Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. J. Affect. Disord.,  2018, 227, 330-337.
[http://dx.doi.org/10.1016/j.jad.2017.11.020] [PMID:  29136602] 
[255] 
Georgiadou, G.; Tarantilis, P.A.; Pitsikas, N. Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder. Neurosci. Lett.,  2012, 528(1), 27-30.
[http://dx.doi.org/10.1016/j.neulet.2012.08.081] [PMID:  22985509] 
[256] 
Wang, Y.; Han, T.; Zhu, Y.; Zheng, C.J.; Ming, Q.L.; Rahman, K.; Qin, L.P. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J. Nat. Med.,  2010, 64(1), 24-30.
[http://dx.doi.org/10.1007/s11418-009-0360-6] [PMID:  19787421] 
[257] 
Sahraian, A.; Jelodar, S.; Javid, Z.; Mowla, A.; Ahmadzadeh, L. Study the effects of saffron on depression and lipid profiles: A double blind comparative study. Asian J. Psychiatr.,  2016, 22, 174-176.
[http://dx.doi.org/10.1016/j.ajp.2015.10.012] [PMID:  26611571] 
[258] 
Lopresti, A.L.; Drummond, P.D. Saffron (Crocus sativus) for depression: A systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum. Psychopharmacol.,  2014, 29(6), 517-527.
[http://dx.doi.org/10.1002/hup.2434] [PMID:  25384672] 
[259] 
Ettehadi, H. Aqueous extract of saffron (Crocus sativus) increases brain dopamine and glutamate concentrations in rats. J. Behav. Brain Sci.,  2013, 3, 315-319.
[260] 
Halataei, B.A.; Khosravi, M.; Arbabian, S.; Sahraei, H.; Golmanesh, L.; Zardooz, H.; Jalili, C.; Ghoshooni, H. Saffron (Crocus sativus) aqueous extract and its constituent crocin reduces stress-induced anorexia in mice. Phytother. Res.,  2011, 25(12), 1833-1838.
[http://dx.doi.org/10.1002/ptr.3495] [PMID:  21503997] 
[261] 
Hooshmandi, Z.; Rohani, A.H.; Eidi, A.; Fatahi, Z.; Golmanesh, L.; Sahraei, H. Reduction of metabolic and behavioral signs of acute stress in male Wistar rats by saffron water extract and its constituent safranal. Pharm. Biol.,  2011, 49(9), 947-954.
[http://dx.doi.org/10.3109/13880209.2011.558103] [PMID:  21592014] 
[262] 
Hassani, F.V. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. Daru,  2014, 22(1), 1-9.
[PMID:  24386961] 
[263] 
Mazidi, M.; Shemshian, M.; Mousavi, S.H.; Norouzy, A.; Kermani, T.; Moghiman, T.; Sadeghi, A.; Mokhber, N.; Ghayour-Mobarhan, M.; Ferns, G.A. A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression. J. Complement. Integr. Med.,  2016, 13(2), 195-199.
[http://dx.doi.org/10.1515/jcim-2015-0043] [PMID:  27101556] 
[264] 
Palacio, J.R.; Markert, U.R.; Martínez, P. Anti-inflammatory properties of N-acetylcysteine on lipopolysaccharide-activated macrophages. Inflamm. Res.,  2011, 60(7), 695-704.
[http://dx.doi.org/10.1007/s00011-011-0323-8] [PMID:  21424515] 
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DOI https://dx.doi.org/10.2174/1570159X20666220103140834	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

The Role of Natural Products in Treatment of Depressive Disorder

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