• APOORVA HA Department of Pharmacology, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.
  • SEEMA MEHDI Department of Pharmacology, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.
  • KRISHNA KL Department of Pharmacology, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.
  • Nabeel K, Mr Department of Pharmacology, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.


Depression is a condition of no mood and loss of interest in any activity that can diminish a person’s thinking, conduct, tendencies, emotional state, and a sense of well-being. Although there is a conventional class of medication which have been beneficial in the treatment of depression, current studies have reported having side effects which can be minimized by the intervention of herbs and phytochemicals. Most of the studies have proven the various mechanisms and have started to research a very ground-breaking method by glancing the ancient treatmen. Where this new approach of using the herbs and phytochemicals has shown better results alone and in combination with conventional drugs which has shown lesser adverse effects. The practice of phytomedicine is an additional option for the treatment of depression. In the various segments of treating the depression, the mainstream can be a breakthrough including phytoconstituents. In this aspect, there are many contributions for the treatment of the depression acting to the neuronal level signaling and the phytoconstituents also have shown some basic mechanisms in the treatment of depression as that of the conventional medications following some primary hypothesis and signaling pathways and life interactions that effects the brain in either way to treat the depression in all sort of way. Clinical evidence is required to provide backing to the safety and effectiveness of herbs and phytochemicals alone or in combination with currently available drugs to overcome the reported side effects during the treatment of depression.

Keywords: Phyto constituents, Interventional therapy, Phyto medicine


1. Gabrilovich E, Markovitch S. Computing Semantic Relatedness using Wikipedia-Based Explicit Semantic Analysis. Haifa, Israel: IJCAI; 2007. p. 1606-11.
2. 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:e61052.
3. Nabavi SM, Daglia M, Braidy N, Nabavi SF. Natural products, micronutrients, and nutraceuticals for the treatment of depression: A short review. Nutr Neurosci 2017;20:180-94.
4. Maxhuni A, Muñoz-Meléndez A, Osmani V, Perez H, Mayora O, Morales EF. Classification of bipolar disorder episodes based on analysis of voice and motor activity of patients. Pervasive Mob Comput 2016;31:50-66.
5. Hasler G. Pathophysiology of depression: Do we have any solid evidence of interest to clinicians? World Psychiatry 2010;9:155-61.
6. Organization WH. Women’s Mental Health: An Evidence Based Review. Geneva: World Health Organization; 2000.
7. Yang L, Zhao Y, Wang Y, Liu L, Zhang X, Li B, et al. The effects of psychological stress on depression. Curr Neuropharmacol 2015;13:494 504.
8. Berton O, Nestler EJ. New approaches to antidepressant drug discovery: Beyond monoamines. Nat Rev Neurosci 2006;7:137-51.
9. Patil N, Rao KN, Balaji O, Naaz H, Baiju G, Naik A, et al. Myxedema madness: An intriguing case of depression in hypothyroidism. Asian J Pharm Clin Res 2017;10:8-9.
10. Duman RS. Neural plasticity: Consequences of stress and actions of antidepressant treatment. Dialogues Clin Neurosci 2004;6:157-69.
11. Eisch AJ, Bolaños CA, de Wit J, Simonak RD, Pudiak CM, Barrot M, et al. Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: A role in depression. Biol Psychiatry 2003;54:994 1005.
12. Gutiérrez B, Pintor L, Gastó C, Rosa A, Bertranpetit J, Vieta E, et al. Variability in the serotonin transporter gene and increased risk for major depression with melancholia. Hum Genet 1998;103:319-22.
13. Reiche EM, Nunes SO, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol 2004;5:617-25.
14. Delgado PL. Depression: The case for a monoamine deficiency. J Clin Psychiatry 2000;61 Suppl 6:7-11.
15. Duman RS, Li N. A neurotrophic hypothesis of depression: Role of synaptogenesis in the actions of NMDA receptor antagonists. Philos Trans R Soc Lond B Biol Sci 2012;367:2475-84.
16. Souêtre E, Salvati E, Belugou JL, Pringuey D, Candito M, Krebs B, et al. Circadian rhythms in depression and recovery: Evidence for blunted amplitude as the main chronobiological abnormality. Psychiatry Res 1989;28:263-78.
17. Machado-Vieira R, Henter ID, Zarate CA Jr. New targets for rapid antidepressant action. Prog Neurobiol 2017;152:21-37.
18. Huang YJ, Lane HY, Lin CH. New treatment strategies of depression: Based on mechanisms related to neuroplasticity. Neural Plast 2017;2017:4605971.
19. Valentine GW, Mason GF, Gomez R, Fasula M, Watzl J, Pittman B, et al. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res 2011;191:122-7.
20. Menniti FS, Pagnozzi MJ, Butler P, Chenard BL, Jaw-Tsai SS, Frost White W, et al. CP-101,606, an NR2B subunit selective NMDA receptor antagonist, inhibits NMDA and injury induced c-fos expression and cortical spreading depression in rodents. Neuropharmacology 2000;39:1147-55.
21. Louderback KM, Wills TA, Muglia LJ, Winder DG. Knockdown of BNST gluN2B-containing NMDA receptors mimics the actions of ketamine on novelty-induced hypophagia. Transl Psychiatry 2013;3:e331.
22. Kochlamazashvili G, Bukalo O, Senkov O, Salmen B, Gerardy-Schahn R, Engel AK, et al. Restoration of synaptic plasticity and learning in young and aged NCAM-deficient mice by enhancing neurotransmission mediated by gluN2A-containing NMDA receptors. J Neurosci 2012;32:2263-75.
23. Rouaud E, Billard JM. D-cycloserine facilitates synaptic plasticity but impairs glutamatergic neurotransmission in rat hippocampal slices. Br J Pharmacol 2003;140:1051-6.
24. Heresco-Levy U, Javitt DC, Gelfin Y, Gorelik E, Bar M, Blanaru M, et al. Controlled trial of D-cycloserine adjuvant therapy for treatment-resistant major depressive disorder. J Affect Disord 2006;93:239-43.
25. Keller M, Montgomery S, Ball W, Morrison M, Snavely D, Liu G, et al. Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 2006;59:216-23.
26. Lutter M, Krishnan V, Russo SJ, Jung S, McClung CA, Nestler EJ, et al. Orexin signaling mediates the antidepressant-like effect of calorie restriction. J Neurosci 2008;28:3071-5.
27. Husaini BA. Predictors of depression among the elderly: Racial differences over time. Am J Orthopsychiatry 1997;67:48-58.
28. Moreno-Domínguez S, Rodríguez-Ruiz S, Fernández-Santaella MC, Ortega-Roldán B, Cepeda-Benito A. Impact of fasting on food craving, mood and consumption in bulimia nervosa and healthy women participants. Eur Eat Disord Rev 2012;20:461-7.
29. Hussin NM, Shahar S, Teng NI, Ngah WZ, Das SK. Efficacy of fasting and calorie restriction (FCR) on mood and depression among ageing men. J Nutr Health Aging 2013;17:674-80.
30. Connolly KR, Helmer A, Cristancho MA, Cristancho P, O’Reardon JP. Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: Results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatry 2012;73:e567-73.
31. George MS, Taylor JJ, Short EB. The expanding evidence base for rTMS treatment of depression. Curr Opin Psychiatry 2013;26:13-8.
32. Balaji O, Bairy KL, Veena N. Management of depression in terminally ill patients-a critical review. Asian J Pharm Clin Res 2017;10:31-6.
33. Chollet L, Saboural P, Chauvierre C, Villemin JN, Letourneur D, Chaubet F, et al. Fucoidans in nanomedicine. Mar Drugs 2016;14: e145.
34. Owens MJ. Selectivity of antidepressants: From the monoamine hypothesis of depression to the SSRI revolution and beyond. J Clin Psychiatry 2004;65 Suppl 4:5-10.
35. Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, et al. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: Literature review and implications for clinical applications. JAMA 2005;293:2372-83.
36. Hindmarch I. Beyond the monoamine hypothesis: Mechanisms, molecules and methods. Eur Psychiatry 2002;17 Suppl 3:294-9.
37. De Kloet ER, Vreugdenhil E, Oitzl MS, Joëls M. Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998;19:269-301.
38. Gurib-Fakim A. Medicinal plants: Traditions of yesterday and drugs of tomorrow. Mol Aspects Med 2006;27:1-93.
39. Zhang Q, Shi Y, Ma L, Yi X, Ruan J. Metabolomic analysis using ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF MS) uncovers the effects of light intensity and temperature under shading treatments on the metabolites in tea. PLoS One 2014;9:e112572.
40. Teng J, Zhou W, Zeng Z, Zhao W, Huang Y, Zhang X, et al. Quality components and antidepressant-like effects of GABA green tea. Food Funct 2017;8:3311-8.
41. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.
42. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John’s Wort) in depression: A meta-analysis. J Affect Disord 2017;210:211-21.
43. Russo E, Scicchitano F, Whalley BJ, Mazzitello C, Ciriaco M, Esposito S, et al. Hypericum perforatum: Pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions. Phytother Res 2014;28:643-55.
44. Dell’Aica I, Garbisa S, Caniato R. The renaissance of Hypericum perforatum: Biomedical research catches up with folk medicine. Curr Bioact Compd 2007;3:109-19.
45. Chen SL, Chen CH. Effects of lavender tea on fatigue, depression, and maternal-infant attachment in sleep-disturbed postnatal women. Worldviews Evid Based Nurs 2015;12:370-9.
46. Effati-Daryani F, Mohammad-Alizadeh-Charandabi S, Mirghafourvand M, Taghizadeh M, Mohammadi A. Effect of lavender cream with or without foot-bath on anxiety, stress and depression in pregnancy: A randomized placebo-controlled trial. J Caring Sci 2015;4:63-73.
47. López V, Nielsen B, Solas M, Ramírez MJ, Jäger AK. Exploring pharmacological mechanisms of lavender (Lavandula angustifolia) essential oil on central nervous system targets. Front Pharmacol 2017;8:280.
48. Chen L, Wang X, Lin ZX, Dai JG, Huang YF, Zhao YN, et al. Preventive effects of ginseng total saponins on chronic corticosterone-induced impairment in astrocyte structural plasticity and hippocampal atrophy. Phytother Res 2017;31:1341-8.
49. Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA. Protective effects of ginseng on neurological disorders. Front Aging Neurosci 2015;7:129.
50. Lee S, Rhee DK. Effects of ginseng on stress-related depression, anxiety, and the hypothalamic-pituitary-adrenal axis. J Ginseng Res 2017;41:589-94.
51. Lin SH, Chou ML, Chen WC, Lai YS, Lu KH, Hao CW, et al. A medicinal herb, Melissa officinalis L. Ameliorates depressive-like behavior of rats in the forced swimming test via regulating the serotonergic neurotransmitter. J Ethnopharmacol 2015;175:266-72.
52. Haybar H, Javid AZ, Haghighizadeh MH, Valizadeh E, Mohaghegh SM, Mohammadzadeh A, et al. The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina. Clin Nutr ESPEN 2018;26:47-52.
53. Hershoff A, Rotelli A. Herbal Remedies: A Quick and Easy Guide to Common Disorders and Their Herbal Treatments. United States: Penguin Putnam Inc.; 2001.
54. Sathyapalan T, Beckett S, Rigby AS, Mellor DD, Atkin SL. High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome. Nutr J 2010;9:55.
55. Peters JC. Tryptophan nutrition and metabolism: An overview. Adv Exp Med Biol 1991;294:345-58.
56. Gannon JM, Forrest PE, Roy Chengappa KN. Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder. J Ayurveda Integr Med 2014;5:241-5.
57. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: An experimental study. Phytomedicine 2000;7:463-9.
58. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (Ashwagandha): A review. Altern Med Rev 2000;5:334-46.
59. Olsson EM, von Schéele B, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med 2009;75:105-12.
60. Mao JJ, Xie SX, Zee J, Soeller I, Li QS, Rockwell K, et al. Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial. Phytomedicine 2015;22:394-9.
61. Cropley M, Banks AP, Boyle J. The effects of Rhodiola rosea L. Extract on anxiety, stress, cognition and other mood symptoms. Phytother Res 2015;29:1934-9.
62. Hidese S, Ota M, Wakabayashi C, Noda T, Ozawa H, Okubo T, et al. Effects of chronic l-theanine administration in patients with major depressive disorder: An open-label study. Acta Neuropsychiatr 2017;29:72-9.
63. Shen M, Yang Y, Wu Y, Zhang B, Wu H, Wang L, et al. L-theanine ameliorate depressive-like behavior in a chronic unpredictable mild stress rat model via modulating the monoamine levels in limbic-cortical-striatal-pallidal-thalamic-circuit related brain regions. Phytother Res 2019;33:412-21.
64. Ogawa S, Ota M, Ogura J, Kato K, Kunugi H. Effects of L-theanine on anxiety-like behavior, cerebrospinal fluid amino acid profile, and hippocampal activity in Wistar Kyoto rats. Psychopharmacology (Berl) 2018;235:37-45.
65. Rajkowska G, Stockmeier CA. Astrocyte pathology in major depressive disorder: Insights from human postmortem brain tissue. Curr Drug Targets 2013;14:1225-36.
66. Zhou X, Li Y, Shi X, Ma C. An overview on therapeutics attenuating amyloid ? level in Alzheimer’s disease: Targeting neurotransmission, inflammation, oxidative stress and enhanced cholesterol levels. Am J Transl Res 2016;8:246-69.
67. Trabace L, Zotti M, Morgese MG, Tucci P, Colaianna M, Schiavone S, et al. Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats. Toxicol Appl Pharmacol 2011;255:169-75.
68. Amiresmaeili A, Roohollahi S, Mostafavi A, Askari N. Effects of oregano essential oil on brain TLR4 and TLR2 gene expression and depressive-like behavior in a rat model. Res Pharm Sci 2018;13:130 41.
69. Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: A meta-analysis. J Am Med Dir Assoc 2017;18:503-8.
70. Lopresti AL, Drummond PD. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. J Affect Disord 2017;207:188-96.
71. He X, Yang L, Wang M, Zhuang X, Huang R, Zhu R, et al. Targeting the endocannabinoid/CB1 receptor system for treating major depression through antidepressant activities of curcumin and dexanabinol-loaded solid lipid nanoparticles. Cell Physiol Biochem 2017;42:2281-94.
72. Lopresti AL. Curcumin for neuropsychiatric disorders: A review of in vitro, animal and human studies. J Psychopharmacol 2017;31:287 302.
73. Gracious BL, Gurumurthy S, Cottle A, McCabe TM. Complementary and Alternative Medicine in Child and Adolescent Bipolar Disorder. Oxford: Oxford University Press. Available from: [Last accessed on 2019 Mar 20].
74. Ferulic Acid Supplementation for Management of Depression in Epilepsy. Springer Link. Available from: [Last accessed on 2019 Mar 20].
75. Zeni AL, Camargo A, Dalmagro AP. Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice. Steroids 2017;125:131-6.
76. Liu YM, Shen JD, Xu LP, Li HB, Li YC, Yi LT, et al. Ferulic acid inhibits neuro-inflammation in mice exposed to chronic unpredictable mild stress. Int Immunopharmacol 2017;45:128-34.
77. Jiang X, Liu J, Lin Q, Mao K, Tian F, Jing C, et al. Proanthocyanidin prevents lipopolysaccharide-induced depressive-like behavior in mice via neuroinflammatory pathway. Brain Res Bull 2017;135:40-6.
78. Abhijit S, Subramanyam MV, Devi SA. Grape seed proanthocyanidin and swimming exercise protects against cognitive decline: A study on M1 acetylcholine receptors in aging male rat brain. Neurochem Res 2017;42:3573-86.
79. Xu Y, Wang Z, You W, Zhang X, Li S, Barish PA, et al. Antidepressant like effect of trans-resveratrol: Involvement of serotonin and noradrenaline system. Eur Neuropsychopharmacol 2010;20:405-13.
80. Chen LW, Wang YQ, Wei LC, Shi M, Chan YS. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson’s disease. CNS Neurol Disord Drug Targets 2007;6:273-81.
81. El-Shitany NA, Eid B. Proanthocyanidin protects against cisplatin induced oxidative liver damage through inhibition of inflammation and NF-??/TLR-4 pathway. Environ Toxicol 2017;32:1952-63.
82. Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000;63:1035-42.
83. Moore A, Beidler J, Hong MY. Resveratrol and depression in animal models: A systematic review of the biological mechanisms. Molecules 2018;23: e2197.
84. Ali SH, Madhana RM, Kasala ER, Bodduluru LN, Pitta S, Mahareddy JR, et al. Resveratrol ameliorates depressive-like behavior in repeated corticosterone-induced depression in mice. Steroids 2015;101:37-42.
85. Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci U S A 2007;104:7217-22.
381 Views | 328 Downloads
How to Cite
APOORVA HA, SEEMA MEHDI, KRISHNA KL, and NABEEL K. “MEDICINAL HERBS AND PHYTOCHEMICALS USED IN THE TREATMENT OF DEPRESSION: A REVIEW”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 5, Mar. 2019, pp. 8-14, doi:10.22159/ajpcr.2019.v12i5.32708.
Review Article(s)