Abstract :

Depression is a global mental health challenge with significant social and economic burdens. While conventional pharmacological treatments have been the cornerstone in depression management, there is a growing interest in exploring alternative and complementary herbal therapies. Herbal interventions have emerged as promising therapeutic approaches for depression treatment. Both clinical and preclinical research has shown that individuals with depression often experience simultaneous activation of neuro-inflammatory response within immune system and heightened activity in hypothalamus pituitary-adrenal (HPA) axis of  neuroendocrine system. These two systems interact with each other bidirectionally through neural, immunological and humoral mechanisms. This review article provides an outline of the current progress of research on herbal interventions, emphasizing their potential as emerging therapeutics for depression. It discusses the mechanisms of action, safety profiles, and evidence from clinical studies supporting the use of various herbal remedies. Herbal interventions and traditional Chinese formulations hold promise as a valuable adjunct or alternative to conventional treatments, offering new avenues for the comprehensive care of individuals with depression.

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Keywords :

Chinese medicine, Depression, Herbal, signaling., therapeutic

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References :

1. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). Jama 2003; 289: 3095-3105.
2. Knapen J, Vancampfort D, Moriën Y, Marchal Y. Exercise therapy improves both mental and physical health in patients with major depression. Disabil Rehabil. 2015;37(16):1490-1495. doi:10.3109/09638288.2014.972579
3. López-Muñoz F, Alamo C. Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des 2009; 15: 1563-1586.
4. Castrén E, Monteggia LM. Brain-Derived Neurotrophic Factor Signaling in Depression and Antidepressant Action. Biol Psychiatry. 2021;90(2):128-136.
5. Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM. Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):722-729.
6. Kohler O, Krogh J, Mors O, Benros ME. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment. Curr Neuropharmacol. 2016;14(7):732-742.
7. Fogaça MV, Duman RS. Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions. Front Cell Neurosci. 2019;13:87.
8. Li C, Huang B, Zhang YW. Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network. Pharmaceuticals (Basel). 2021;14(1):65.
9. Li C, Huang J, Cheng YC, Zhang YW. Traditional Chinese Medicine in Depression Treatment: From Molecules to Systems. Front Pharmacol. 2020;11:586
10. Yeung WF, Chung KF, Ng KY, Yu YM, Zhang SP, et al. Prescription of Chinese Herbal Medicine in Pattern-Based Traditional Chinese Medicine Treatment for Depression: A Systematic Review. Evid Based Complement Alternat Med 2015; 2015: 160189.
11. Lange KW, Nakamura Y, Lange KM, Zhao H. Tea and depression. Food Science and Human Wellness 2022; 11: 476-482.
12. Sobolewska-Nowak J, Wachowska K, Nowak A, Orzechowska A, Szulc A, et al. Exploring the Heart-Mind Connection: Unraveling the Shared Pathways between Depression and Cardiovascular Diseases. Biomedicines 2023; 11.
13. Gasmi A, Nasreen A, Menzel A, Gasmi Benahmed A, Pivina L, et al. Neurotransmitters Regulation and Food Intake: The Role of Dietary Sources in Neurotransmission. Molecules 2022; 28.
14. Prah A, Purg M, Stare J, Vianello R, Mavri J. How Monoamine Oxidase A Decomposes Serotonin: An Empirical Valence Bond Simulation of the Reactive Step. J Phys Chem B 2020; 124: 8259-8265.
15. Hirschfeld RM. History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry. 2000;61 Suppl 6:4-6.
16. Cavaleri D, Moretti F, Bartoccetti A, Mauro S, Crocamo C, et al. The role of BDNF in major depressive disorder, related clinical features, and antidepressant treatment: Insight from meta-analyses. Neurosci Biobehav Rev 2023; 149: 105159.
17. Guzzetta KE, Cryan JF, O’Leary OF. Microbiota-Gut-Brain Axis Regulation of Adult Hippocampal Neurogenesis. Brain Plast. 2022;8(1):97-119.
18. Correia AS, Cardoso A, Vale N. BDNF Unveiled: Exploring Its Role in Major Depression Disorder Serotonergic Imbalance and Associated Stress Conditions. Pharmaceutics. 2023;15(8):2081.
19. Chen X, Jiang F, Yang Q, Zhang P, Zhu H, et al. Bilateral repetitive transcranial magnetic stimulation ameliorated sleep disorder and hypothalamic-pituitary-adrenal axis dysfunction in subjects with major depression. Front Psychiatry 2022; 13: 951595.

 

20. Rashid S, Gulfam A, Noor TA, Yaseen K, Sheikh MAA, et al. Anxiety and Depression in Heart Failure: An Updated Review. Curr Probl Cardiol 2023; 48: 101987.
21. Li B, Yang W, Ge T, Wang Y, Cui R. Stress induced microglial activation contributes to depression. Pharmacol Res. 2022;179:106145.
22. Aleem D, Tohid H. Pro-inflammatory Cytokines, Biomarkers, Genetics and the Immune System: A Mechanistic Approach of Depression and Psoriasis. Rev Colomb Psiquiatr (Engl Ed). 2018;47(3):177-186.
23. Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med. 2015;3(10):136.
24. Sanacora G, Treccani G, Popoli M. Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology. 2012;62(1):63-77.
25. Blanke ML, VanDongen AMJ. Activation Mechanisms of the NMDA Receptor. In: Van Dongen AM, ed. Biology of the NMDA Receptor. Boca Raton (FL): CRC Press/Taylor & Francis; 2009.
26. McGrath T, Baskerville R, Rogero M, Castell L. Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases. Nutrients. 2022;14(5):917.
27. Niciu MJ, Henter ID, Luckenbaugh DA, Zarate CA Jr, Charney DS. Glutamate receptor antagonists as fast-acting therapeutic alternatives for the treatment of depression: ketamine and other compounds. Annu Rev Pharmacol Toxicol. 2014;54:119-139.
28. Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16(4):383-406.
29. Richards A, Kanady JC, Neylan TC. Sleep disturbance in PTSD and other anxiety-related disorders: an updated review of clinical features, physiological characteristics, and psychological and neurobiological mechanisms [published correction appears in Neuropsychopharmacology. 2019 Oct 7;:]. Neuropsychopharmacology. 2020;45(1):55-73.
30. Sahoo S, S B. Pharmacogenomic assessment of herbal drugs in affective disorders. Biomed Pharmacother. 2019;109:1148-1162.
31. Young JF, Miller MR, Khan N. Screening and managing depression in adolescents. Adolesc Health Med Ther. 2010;1:87-95.
32. Tóth B, Hegyi P, Lantos T, Szakács Z, Kerémi B, et al. The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis. Planta Med 2019; 85: 24-31.
33. Zandi N, Pazoki B, Momeni Roudsari N, Lashgari NA, Jamshidi V, et al. Prospects of Saffron and its Derivatives in Alzheimer’s Disease. Arch Iran Med 2021; 24: 233-252.
34. Siddiqui SA, Ali Redha A, Snoeck ER, Singh S, Simal-Gandara J, et al. Anti-Depressant Properties of Crocin Molecules in Saffron. Molecules 2022; 27.
35. Ivanova Stojcheva E, Quintela JC. The Effectiveness of Rhodiola rosea L. Preparations in Alleviating Various Aspects of Life-Stress Symptoms and Stress-Induced Conditions-Encouraging Clinical Evidence. Molecules. 2022;27(12):3902.
36. Ravindran AV, Balneaves LG, Faulkner G, Ortiz A, McIntosh D, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments. Can J Psychiatry 2016; 61: 576-587.
37. Carradori S, D’Ascenzio M, Chimenti P, Secci D, Bolasco A. Selective MAO-B inhibitors: a lesson from natural products. Mol Divers. 2014;18(1):219-243.
38. Amsterdam JD, Panossian AG. Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine. 2016;23(7):770-783.
39. Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci. 2017;1401(1):49-64.
40. Raju M, Kulkarni YA, Wairkar S. Therapeutic potential and recent delivery systems of berberine: A wonder molecule. Journal of Functional Foods. 2019;61:103517.
41. Fan J, Zhang K, Jin Y, Li B, Gao S, et al. Pharmacological effects of berberine on mood disorders. J Cell Mol Med 2019; 23: 21-28.
42. Mujtaba MA, Akhter MH, Alam MS, Ali MD, Hussain A. An Updated Review on Therapeutic Potential and Recent Advances in Drug Delivery of Berberine: Current Status and Future Prospect. Curr Pharm Biotechnol. 2022;23(1):60-71.
43. Mithaiwala MN, Santana-Coelho D, Porter GA, O’Connor JC. Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications. Cells. 2021;10(6):1548.
44. Deng C, Chen H, Meng Z, Meng S. Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment. Front Endocrinol (Lausanne). 2022;13:955618.
45. Behl T, Singh S, Sharma N, Zahoor I, Albarrati A, et al. Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine: Current and Future Trends. Molecules 2022; 27.
46. Yi LT, Li CF, Zhan X, Cui CC, Xiao F, et al. Involvement of monoaminergic system in the antidepressant-like effect of the flavonoid naringenin in mice. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1223-1228.
47. Pannu A, Sharma PC, Thakur VK, Goyal RK. Emerging Role of Flavonoids as the Treatment of Depression. Biomolecules. 2021;11(12):1825.
48. German-Ponciano LJ, Rosas-Sánchez GU, Rivadeneyra-Domínguez E, Rodríguez-Landa JF. Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents. Scientifica (Cairo). 2018;2018:2963565.
49. Neshatdoust S, Saunders C, Castle SM, Vauzour D, Williams C, et al. High-flavonoid intake induces cognitive improvements linked to changes in serum brain-derived neurotrophic factor: Two randomised, controlled trials. Nutr Healthy Aging 2016; 4: 81-93.
50. Stohs SJ, Chen O, Ray SD, Ji J, Bucci LR, et al. Highly Bioavailable Forms of Curcumin and Promising Avenues for Curcumin-Based Research and Application: A Review. Molecules. 2020;25(6):1397.
51. Lee B, Lee H. Systemic Administration of Curcumin Affect Anxiety-Related Behaviors in a Rat Model of Posttraumatic Stress Disorder via Activation of Serotonergic Systems. Evid Based Complement Alternat Med. 2018;2018:9041309.
52. Fan C, Song Q, Wang P, Li Y, Yang M, et al. Neuroprotective Effects of Curcumin on IL-1β-Induced Neuronal Apoptosis and Depression-Like Behaviors Caused by Chronic Stress in Rats. Front Cell Neurosci. 2019;12:516.
53. Dionisie V, Filip GA, Manea MC, Manea M, Riga S. The anti-inflammatory role of SSRI and SNRI in the treatment of depression: a review of human and rodent research studies. Inflammopharmacology. 2021;29(1):75-90.
54. Afshari AR, Fanoudi S, Rajabian A, Sadeghnia HR, Mollazadeh H, et al. Potential protective roles of phytochemicals on glutamate-induced neurotoxicity: A review. Iran J Basic Med Sci. 2020;23(9):1113-1123.
55. Kang D, Dong H, Shen Y, Ou J, Zhao J. The clinical application of Chinese herbal medication to depression: A narrative review. Front Public Health. 2023;11:1120683.
56. Liu L, Liu C, Wang Y, Wang P, Li Y, et al. Herbal Medicine for Anxiety, Depression and Insomnia. Curr Neuropharmacol. 2015;13(4):481-493.
57. Ravipati AS, Zhang L, Koyyalamudi SR, Jeong SC, Reddy N, et al. Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content. BMC Complement Altern Med 2012; 12: 173.
58. Vickers A, Zollman C. ABC of complementary medicine: herbal medicine. Bmj 1999; 319: 1050-1053.
59. Yu Y, Zhang G, Han T, Huang H. Analysis of the pharmacological mechanism of Banxia Xiexin decoction in treating depression and ulcerative colitis based on a biological network module. BMC Complement Med Ther. 2020;20(1):199.
60. Chen L, Wei S, He Y, Wang X, He T, et al. Treatment of Chronic Gastritis with Traditional Chinese Medicine: Pharmacological Activities and Mechanisms. Pharmaceuticals (Basel) 2023; 16.
61. Sun J, Ren J, Hu X, Hou Y, Yang Y. Therapeutic effects of Chinese herbal medicines and their extracts on diabetes. Biomed Pharmacother. 2021;142:111977.
62. Yamada T, Wajima T, Nakaminami H, Kobayashi K, Ikoshi H, et al. The modified Gingyo-san, a Chinese herbal medicine, has direct antibacterial effects against respiratory pathogens. BMC Complement Altern Med. 2016;16(1):463.
63. Sarkar A, Sarmah D, Datta A, Kaur H, Jagtap P, et al. Post-stroke depression: Chaos to exposition. Brain Res Bull 2021; 168: 74-88.
64. Kwon CY, Lee B, Chung SY, Kim JW, Shin A, et al. Efficacy and safety of Sihogayonggolmoryeo-tang (Saikokaryukotsuboreito, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) for post-stroke depression: A systematic review and meta-analysis. Sci Rep 2019; 9: 14536.

 

65. Culang-Reinlieb ME, Johnert LC, Brickman AM, Steffens DC, Garcon E, et al. MRI-defined vascular depression: a review of the construct. Int J Geriatr Psychiatry. 2011;26(11):1101-1108.
66. Pan J, Lei X, Wang J, Huang S, Wang Y, et al. Effects of Kaixinjieyu, a Chinese herbal medicine preparation, on neurovascular unit dysfunction in rats with vascular depression. BMC Complement Altern Med 2015; 15: 291.
67. Crișan I, Ona A, Vârban D, Muntean L, Vârban R, et al. Current Trends for Lavender (Lavandula angustifolia Mill.) Crops and Products with Emphasis on Essential Oil Quality. Plants (Basel) 2023; 12.
68. Perry R, Terry R, Watson LK, Ernst E. Is lavender an anxiolytic drug? A systematic review of randomised clinical trials. Phytomedicine. 2012;19(8-9):825-835.
69. Araj-Khodaei M, Noorbala AA, Yarani R, Emadi F, Emaratkar E, et al. A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression. BMC Complement Med Ther 2020; 20: 207.
70. Akhondzadeh S, Kashani L, Fotouhi A, Jarvandi S, Mobaseri M, et al. Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression: a double-blind, randomized trial. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 123-127.
71. Graham PH, Browne L, Cox H, Graham J. Inhalation aromatherapy during radiotherapy: results of a placebo-controlled double-blind randomized trial. J Clin Oncol. 2003;21(12):2372-2376.
72. Linde K, Berner M, Egger M, Mulrow C. St John’s wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatry. 2005;186:99-107.
73. Butterweck V. Mechanism of action of St John’s wort in depression : what is known?. CNS Drugs. 2003;17(8):539-562.
74. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):118-127.
75. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999;58(11):1685-1693.
76. Nah SY, Kim DH, Rhim H. Ginsenosides: are any of them candidates for drugs acting on the central nervous system?. CNS Drug Rev. 2007;13(4):381-404.
77. Lee E, Kim S, Chung KC, Choo MK, Kim DH, et al. 20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons. Eur J Pharmacol 2006; 536: 69-77.
78. Choi JY, Woo TS, Yoon SY, Ike Campomayor Dela P, Choi YJ, et al. Red ginseng supplementation more effectively alleviates psychological than physical fatigue. J Ginseng Res 2011; 35: 331-338.

 

79. Xu C, Teng J, Chen W, Ge Q, Yang Z, et al. 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1402-1411.
80. Jiang N, Zhang Y, Yao C, Huang H, Wang Q, et al. Ginsenosides Rb1 Attenuates Chronic Social Defeat Stress-Induced Depressive Behavior via Regulation of SIRT1-NLRP3/Nrf2 Pathways. Front Nutr 2022; 9: 868833.
81. Jin Y, Cui R, Zhao L, Fan J, Li B. Mechanisms of Panax ginseng action as an antidepressant. Cell Prolif. 2019;52(6):e12696.
82. Vigna L, Morelli F, Agnelli GM, Napolitano F, Ratto D, et al. Hericium erinaceus Improves Mood and Sleep Disorders in Patients Affected by Overweight or Obesity: Could Circulating Pro-BDNF and BDNF Be Potential Biomarkers? Evid Based Complement Alternat Med 2019; 2019: 7861297.
83. Chong PS, Fung ML, Wong KH, Lim LW. Therapeutic Potential of Hericium erinaceus for Depressive Disorder. Int J Mol Sci. 2019;21(1):163.
84. Kushairi N, Phan CW, Sabaratnam V, David P, Naidu M. Lion’s Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. Suppresses H2O2-Induced Oxidative Damage and LPS-Induced Inflammation in HT22 Hippocampal Neurons and BV2 Microglia. Antioxidants (Basel). 2019;8(8):261.
85. Lin PY. Regulation of proteolytic cleavage of brain-derived neurotrophic factor precursor by antidepressants in human neuroblastoma cells. Neuropsychiatr Dis Treat. 2015;11:2529-2532.