Chinese Herbal Medicine for Depression: Comparison
Please note this is a comparison between Version 2 by Karina Chen and Version 1 by Chan Li.

Depression is a mood disorder that causes a loss of interest and constant sadness. Central nervous system (CNS)-targeted medications alone are insufficient for the treatment of depression. Multidrug and multitarget Chinese Herbal Medicine (CHM) has great potential to assist in the development of novel medications for the systematic and effective pharmacotherapy of depression.

  • Chinese herbal medicine
  • depression
  • neuroimmune system
  • neuroendocrine system
  • neuroendocrine-immune network
  • neuroinflammation
  • HPA axis
Please wait, diff process is still running!

References

  1. WHO. Depression. Available online: https://www.who.int/news-room/fact-sheets/detail/depression (accessed on January 30, 2020)
  2. Pothula, S.; Kato, T.; Liu, R.J.; Wu, M.; Gerhard, D.; Shinohara, R.; Sliby, A.N.; Chowdhury, G.M.; Behar, K.L.; Sanacora, G.; et al. Cell-Type specific modulation of NMDA receptors triggers antidepressant actions. Mol. Psychiatry 2020, doi:10.1038/s41380-020-0796-3.
  3. Jiang, C.Y.; Qin, X.Y.; Yuan, M.M.; Lu, G.J.; Cheng, Y. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside Reverses Stress-Induced Depression via Inflammatory and Oxidative Stress Pathways. Oxid. Med. Cell. Longev. 2018, 2018, 9501427, doi:10.1155/2018/9501427.
  4. Zhang, Y.W.; Cheng, Y.C. Challenge and Prospect of Traditional Chinese Medicine in Depression Treatment. Front. Neurosci. 2019, 13, 190, doi:10.3389/fnins.2019.00190.
  5. Fogaca, M.V.; Duman, R.S. Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Inter-ventions. Front. Cell. Neurosci. 2019, 13, 87, doi:10.3389/fncel.2019.00087.
  6. Kim, Y.K.; Na, K.S.; Myint, A.M.; Leonard, B.E. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 2016, 64, 277–284, doi:10.1016/j.pnpbp.2015.06.008.
  7. Ignacio, Z.M.; da Silva, R.S.; Plissari, M.E.; Quevedo, J.; Reus, G.Z. Physical Exercise and Neuroinflammation in Major De-pressive Disorder. Mol. Neurobiol. 2019, 56, 8323–8335, doi:10.1007/s12035-019-01670-1.
  8. 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, 722–729, doi:10.1016/j.pnpbp.2010.04.011.
  9. Jiang, Y.Z.; Peng, T.M.; Gaur, U.; Silva, M.; Little, P.; Chen, Z.; Qiu, W.; Zhang, Y.D.; Zheng, W.H. Role of Corticotropin Re-leasing Factor in the Neuroimmune Mechanisms of Depression: Examination of Current Pharmaceutical and Herbal Therapies. Front. Cell. Neurosci. 2019, 13, 290, doi:ARTN 29010.3389/fncel.2019.00290.
  10. Wang, Y.; Li, M.; Liang, Y.; Yang, Y.; Liu, Z.; Yao, K.; Chen, Z.; Zhai, S. Chinese Herbal Medicine for the Treatment of De-pression: Applications, Efficacies and Mechanisms. Curr. Pharm. Des. 2017, 23, 5180–5190, doi:10.2174/1381612823666170918120018.
  11. Feng, D.D.; Tang, T.; Lin, X.P.; Yang, Z.Y.; Yang, S.; Xia, Z.A.; Wang, Y.; Zheng, P.; Wang, Y.; Zhang, C.H. Nine traditional Chinese herbal formulas for the treatment of depression: An ethnopharmacology, phytochemistry, and pharmacology review. Neuropsychiatr. Dis. Treat. 2016, 12, 2387–2402, doi:10.2147/NDT.S114560.
  12. Li, C.; Huang, J.; Cheng, Y.C.; Zhang, Y.W. Traditional Chinese Medicine in Depression Treatment: From Molecules to Systems. Front. Pharmacol. 2020, 11, 586, doi:10.3389/fphar.2020.00586.
  13. Chen, G.; Guo, X. Neurobiology of Chinese Herbal Medicine on Major Depressive Disorder. Int. Rev. Neurobiol. 2017, 135, 77–95, doi:10.1016/bs.irn.2017.02.005.
  14. Yeung, W.F.; Chung, K.F.; Ng, K.Y.; Yu, Y.M.; Zhang, S.P.; Ng, B.F.; Ziea, E.T. 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, doi:10.1155/2015/160189.
  15. Jia, K.K.; Zheng, Y.J.; Zhang, Y.X.; Liu, J.H.; Jiao, R.Q.; Pan, Y.; Kong, L.D. Banxia-Houpu decoction restores glucose intolerance in CUMS rats through improvement of insulin signaling and suppression of NLRP3 inflammasome activation in liver and brain. J. Ethnopharmacol. 2017, 209, 219–229, doi:10.1016/j.jep.2017.08.004.
  16. Yi, L.T.; Li, J.; Liu, B.B.; Li, C.F. Screening of the antidepressant-like effect of the traditional Chinese medicinal formula Si-Ni-San and their possible mechanism of action in mice. Pharmacogn. Res. 2013, 5, 36–42, doi:10.4103/0974-8490.105647.
  17. Zong, Y.; Chen, T.; Dong, H.; Zhu, L.; Ju, W. Si-Ni-San Prevents Reserpine-Induced Depression by Inhibiting Inflammation and Regulating CYP450 Enzymatic Activity. Front. Pharmacol. 2019, 10, 1518, doi:10.3389/fphar.2019.01518.
  18. Smith, R.S. The macrophage theory of depression. Med. Hypotheses 1991, 35, 298–306, doi:10.1016/0306-9877(91)90272-z.
  19. Wohleb, E.S.; Franklin, T.; Iwata, M.; Duman, R.S. Integrating neuroimmune systems in the neurobiology of depression. Nat. Rev. Neurosci. 2016, 17, 497–511, doi:10.1038/nrn.2016.69.
  20. Kohler, O.; Krogh, J.; Mors, O.; Benros, M.E. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment. Curr. Neuropharmacol. 2016, 14, 732–742, doi:10.2174/1570159x14666151208113700.
  21. Zhang, J.C.; Yao, W.; Hashimoto, K. Brain-Derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-Related Depression and Potential Therapeutic Targets. Curr. Neuropharmacol. 2016, 14, 721–731, doi:10.2174/1570159x14666160119094646.
  22. Halaris, A. Inflammation and depression but where does the inflammation come from? Curr. Opin. Psychiatry 2019, 32, 422–428, doi:10.1097/yco.0000000000000531.
  23. Tian, H.; Li, G.; Xu, G.; Liu, J.; Wan, X.; Zhang, J.; Xie, S.; Cheng, J.; Gao, S. Inflammatory cytokines derived from peripheral blood contribute to the modified electroconvulsive therapy-induced cognitive deficits in major depressive disorder. Eur. Arch. Psychiatry Clin. Neurosci. 2020, doi:10.1007/s00406-020-01128-9.
  24. Ng, A.; Tam, W.W.; Zhang, M.W.; Ho, C.S.; Husain, S.F.; McIntyre, R.S.; Ho, R.C. IL-1β, IL-6, TNF-α and CRP in Elderly Patients with Depression or Alzheimer’s disease: Systematic Review and Meta-Analysis. Sci. Rep. 2018, 8, 12050, doi:10.1038/s41598-018-30487-6.
  25. D’Mello, C.; Swain, M.G. Immune-to-Brain Communication Pathways in Inflammation-Associated Sickness and Depression. Curr. Top. Behav. Neurosci. 2017, 31, 73–94, doi:10.1007/7854_2016_37.
  26. Chiu, W.C.; Su, Y.P.; Su, K.P.; Chen, P.C. Recurrence of depressive disorders after interferon-induced depression. Transl. Psychiatry 2017, 7, e1026, doi:10.1038/tp.2016.274.
  27. Zhao, Y.; Shang, P.; Wang, M.; Xie, M.; Liu, J. Neuroprotective Effects of Fluoxetine Against Chronic Stress-Induced Neural Inflammation and Apoptosis: Involvement of the p38 Activity. Front. Physiol. 2020, 11, 351, doi:10.3389/fphys.2020.00351.
  28. Wang, M.; Yan, S.; Zhou, Y.; Xie, P. trans-Cinnamaldehyde Reverses Depressive-Like Behaviors in Chronic Unpredictable Mild Stress Rats by Inhibiting NF-κB/NLRP3 Inflammasome Pathway. Evid. Based Complement. Alternat. Med. 2020, 2020, 4572185, doi:10.1155/2020/4572185.
  29. Dong, X.Z.; Wang, D.X.; Lu, Y.P.; Yuan, S.; Liu, P.; Hu, Y. Antidepressant effects of Kai-Xin-San in fluoxetine-resistant de-pression rats. Braz. J. Med. Biol. Res. 2017, 50, e6161, doi:10.1590/1414-431X20176161.
  30. Dantzer, R.; O’Connor, J.C.; Lawson, M.A.; Kelley, K.W. Inflammation-Associated depression: From serotonin to kynurenine. Psychoneuroendocrinology 2011, 36, 426–436, doi:10.1016/j.psyneuen.2010.09.012.
  31. Zhang, Z.; Song, Z.; Shen, F.; Xie, P.; Wang, J.; Zhu, A.S.; Zhu, G. Ginsenoside Rg1 Prevents PTSD-Like Behaviors in Mice Through Promoting Synaptic Proteins, Reducing Kir4.1 and TNF-α in the Hippocampus. Mol. Neurobiol. 2020, 1–14, doi:10.1007/s12035-020-02213-9.
  32. Miller, A.H.; Raison, C.L. The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 2016, 16, 22–34, doi:10.1038/nri.2015.5.
  33. Turkheimer, F.E.; Althubaity, N.; Schubert, J.; Nettis, M.A.; Cousins, O.; Dima, D.; Mondelli, V.; Bullmore, E.T.; Pariante, C.; Veronese, M. Increased serum peripheral C-reactive protein is associated with reduced brain barriers permeability of TSPO radioligands in healthy volunteers and depressed patients: Implications for inflammation and depression. Brain Behav. Immun. 2020, 91, 487–497, doi:10.1016/j.bbi.2020.10.025.
  34. Rosenblat, J.D.; Cha, D.S.; Mansur, R.B.; McIntyre, R.S. Inflamed moods: A review of the interactions between inflammation and mood disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 2014, 53, 23–34, doi:10.1016/j.pnpbp.2014.01.013.
  35. Duman, R.S.; Aghajanian, G.K.; Sanacora, G.; Krystal, J.H. Synaptic plasticity and depression: New insights from stress and rapid-acting antidepressants. Nat. Med. 2016, 22, 238–249, doi:10.1038/nm.4050.
  36. Deng, S.L.; Chen, J.G.; Wang, F. Microglia: A Central Player in Depression. Curr. Med. Sci. 2020, 40, 391–400, doi:10.1007/s11596-020-2193-1.
  37. Torres-Platas, S.G.; Cruceanu, C.; Chen, G.G.; Turecki, G.; Mechawar, N. Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain Behav. Immun. 2014, 42, 50–59, doi:10.1016/j.bbi.2014.05.007.
  38. Setiawan, E.; Wilson, A.A.; Mizrahi, R.; Rusjan, P.M.; Miler, L.; Rajkowska, G.; Suridjan, I.; Kennedy, J.L.; Rekkas, P.V.; Houle, S.; et al. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry 2015, 72, 268–275, doi:10.1001/jamapsychiatry.2014.2427.
  39. Zhang, L.; Zhang, J.; You, Z. Switching of the Microglial Activation Phenotype Is a Possible Treatment for Depression Disorder. Front. Cell. Neurosci. 2018, 12, 306, doi:10.3389/fncel.2018.00306.
  40. Brown, G.C. The endotoxin hypothesis of neurodegeneration. J. Neuroinflamm. 2019, 16, 180, doi:10.1186/s12974-019-1564-7.
  41. Bollinger, J.L.; Wohleb, E.S. The formative role of microglia in stress-induced synaptic deficits and associated behavioral con-sequences. Neurosci. Lett. 2019, 711, 134369, doi:10.1016/j.neulet.2019.134369.
  42. Wohleb, E.S.; Terwilliger, R.; Duman, C.H.; Duman, R.S. Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-Like Behavior. Biol. Psychiatry 2018, 83, 38–49, doi:10.1016/j.biopsych.2017.05.026.
  43. Wang, Y.S.; Shen, C.Y.; Jiang, J.G. Antidepressant active ingredients from herbs and nutraceuticals used in TCM: Pharmaco-logical mechanisms and prospects for drug discovery. Pharmacol. Res. 2019, 150, 104520, doi:10.1016/j.phrs.2019.104520.
  44. Guan, F.; Lam, W.; Hu, R.; Kim, Y.K.; Han, H.; Cheng, Y.C. Majority of Chinese Medicine Herb Category “Qing Re Yao” Have Multiple Mechanisms of Anti-inflammatory Activity. Sci. Rep. 2018, 8, 7416, doi:10.1038/s41598-018-25813-x.
  45. Lu, Z.B.; Ou, J.Y.; Cao, H.H.; Liu, J.S.; Yu, L.Z. Heat-Clearing Chinese Medicines in Lipopolysaccharide-Induced Inflammation. Chin. J. Integr. Med. 2020, 26, 552–559, doi:10.1007/s11655-020-3256-7.
  46. Panossian, A.; Brendler, T. The Role of Adaptogens in Prophylaxis and Treatment of Viral Respiratory Infections. Pharmaceu-ticals 2020, 13, 236, doi:10.3390/ph13090236.
  47. Adzic, M.; Brkic, Z.; Mitic, M.; Francija, E.; Jovicic, M.J.; Radulovic, J.; Maric, N.P. Therapeutic Strategies for Treatment of Inflammation-related Depression. Curr. Neuropharmacol. 2018, 16, 176–209, doi:10.2174/1570159X15666170828163048.
  48. Young, J.J.; Bruno, D.; Pomara, N. A review of the relationship between proinflammatory cytokines and major depressive disorder. J. Affect. Disord. 2014, 169, 15–20, doi:10.1016/j.jad.2014.07.032.
  49. Zhang, Z.D.; Li, H.; Wan, F.; Su, X.Y.; Lu, Y.; Chen, D.F.; Zhang, Y.Y. Polysaccharides extracted from the roots of Bupleurum chinense DC modulates macrophage functions. Chin. J. Nat. Med. 2017, 15, 889–898, doi:10.1016/S1875-5364(18)30004-9.
  50. Shiu, L.Y.; Huang, H.H.; Chen, C.Y.; Cheng, H.Y.; Chen, C.I.; Kuo, S.M. Reparative and toxicity-reducing effects of lipo-some-encapsulated saikosaponin in mice with liver fibrosis. Biosci. Rep. 2020, 40, BSR20201219, doi:10.1042/BSR20201219.
  51. Zhang, B.Z.; Guo, X.T.; Chen, J.W.; Zhao, Y.; Cong, X.; Jiang, Z.L.; Cao, R.F.; Cui, K.; Gao, S.S.; Tian, W.R. Saikosaponin-D attenuates heat stress-induced oxidative damage in LLC-PK1 cells by increasing the expression of anti-oxidant enzymes and HSP72. Am. J. Chin. Med. 2014, 42, 1261–1277, doi:10.1142/S0192415X14500797.
  52. Su, J.; Pan, Y.W.; Wang, S.Q.; Li, X.Z.; Huang, F.; Ma, S.P. Saikosaponin-d attenuated lipopolysaccharide-induced depres-sive-like behaviors via inhibiting microglia activation and neuroinflammation. Int. Immunopharmacol. 2020, 80, 106181, doi:10.1016/j.intimp.2019.106181.
  53. Chen, X.Q.; Chen, S.J.; Liang, W.N.; Wang, M.; Li, C.F.; Wang, S.S.; Dong, S.Q.; Yi, L.T.; Li, C.D. Saikosaponin A attenuates perimenopausal depression-like symptoms by chronic unpredictable mild stress. Neurosci. Lett. 2018, 662, 283–289, doi:10.1016/j.neulet.2017.09.046.
  54. Li, J.; Zhao, R.; Li, X.; Sun, W.; Qu, M.; Tang, Q.; Yang, X.; Zhang, S. Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+CD25+ regulatory T cells. Neuropsychiatr. Dis. Treat. 2016, 12, 883–896, doi:10.2147/NDT.S98131.
  55. Su, W.J.; Zhang, Y.; Chen, Y.; Gong, H.; Lian, Y.J.; Peng, W.; Liu, Y.Z.; Wang, Y.X.; You, Z.L.; Feng, S.J.; et al. NLRP3 gene knockout blocks NF-κB and MAPK signaling pathway in CUMS-induced depression mouse model. Behav. Brain Res. 2017, 322, 1–8, doi:10.1016/j.bbr.2017.01.018.
  56. Ji, H.F.; Zhuang, Q.S.; Shen, L. Genetic overlap between type 2 diabetes and major depressive disorder identified by bioin-formatics analysis. Oncotarget 2016, 7, 17410–17414, doi:10.18632/oncotarget.8202.
  57. Wang, M.; Zhou, W.; Zhou, X.; Zhuang, F.; Chen, Q.; Li, M.; Ma, T.; Gu, S. Antidepressant-Like effects of alarin produced by activation of TrkB receptor signaling pathways in chronic stress mice. Behav. Brain Res. 2015, 280, 128–140, doi:10.1016/j.bbr.2014.11.039.
  58. Masson, J.; Emerit, M.B.; Hamon, M.; Darmon, M. Serotonergic signaling: Multiple effectors and pleiotropic effects. Wiley Interdiscip. Rev. Membr. Transp. Signal. 2012, 1, 685–713, doi:10.1002/wmts.50.
  59. Duric, V.; Banasr, M.; Licznerski, P.; Schmidt, H.D.; Stockmeier, C.A.; Simen, A.A.; Newton, S.S.; Duman, R.S. A negative regulator of MAP kinase causes depressive behavior. Nat. Med. 2010, 16, 1328–1332, doi:10.1038/nm.2219.
  60. Welcome, M.O.; Mastorakis, N.E. Stress-Induced blood brain barrier disruption: Molecular mechanisms and signaling path-ways. Pharmacol. Res. 2020, 157, 104769, doi:10.1016/j.phrs.2020.104769.
  61. Chiang, J.J.; Cole, S.W.; Bower, J.E.; Irwin, M.R.; Taylor, S.E.; Arevalo, J.; Fuligni, A. Depressive symptoms and immune transcriptional profiles in late adolescents. Brain Behav. Immun. 2019, 80, 163–169, doi:10.1016/j.bbi.2019.03.004.
  62. Liu, W.; Jiang, H.L.; Cai, L.L.; Yan, M.; Dong, S.J.; Mao, B. Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model. Evid. Based Complement. Alternat. Med. 2016, 2016, 5292346, doi:10.1155/2016/5292346.
  63. Shih, R.H.; Wang, C.Y.; Yang, C.M. NF-κB Signaling Pathways in Neurological Inflammation: A Mini Review. Front. Mol. Neurosci. 2015, 8, 77, doi:10.3389/fnmol.2015.00077.
  64. Lopez-Pedrajas, R.; Ramirez-Lamelas, D.T.; Muriach, B.; Sanchez-Villarejo, M.V.; Almansa, I.; Vidal-Gil, L.; Romero, F.J.; Barcia, J.M.; Muriach, M. Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum. Front. Cell. Neurosci. 2015, 9, 279, doi:10.3389/fncel.2015.00279.
  65. Kaltschmidt, B.; Kaltschmidt, C. NF-κB in the nervous system. Cold Spring Harb. Perspect. Biol. 2009, 1, a001271, doi:10.1101/cshperspect.a001271.
  66. Caviedes, A.; Lafourcade, C.; Soto, C.; Wyneken, U. BDNF/NF-κB Signaling in the Neurobiology of Depression. Curr. Pharm. Des. 2017, 23, 3154–3163, doi:10.2174/1381612823666170111141915.
  67. Pradere, J.P.; Hernandez, C.; Koppe, C.; Friedman, R.A.; Luedde, T.; Schwabe, R.F. Negative regulation of NF-κB p65 activity by serine 536 phosphorylation. Sci. Signal. 2016, 9, ra85, doi:10.1126/scisignal.aab2820.
  68. Koo, J.W.; Russo, S.J.; Ferguson, D.; Nestler, E.J.; Duman, R.S. Nuclear factor-κB is a critical mediator of stress-impaired neu-rogenesis and depressive behavior. Proc. Natl. Acad. Sci. USA 2010, 107, 2669–2674, doi:10.1073/pnas.0910658107.
  69. Bottcher, M.; Muller-Fielitz, H.; Sundaram, S.M.; Gallet, S.; Neve, V.; Shionoya, K.; Zager, A.; Quan, N.; Liu, X.; Schmidt-Ullrich, R.; et al. NF-κB signaling in tanycytes mediates inflammation-induced anorexia. Mol. Metab. 2020, 39, 101022, doi:10.1016/j.molmet.2020.101022.
  70. Jin, Y.; Cui, R.; Zhao, L.; Fan, J.; Li, B. Mechanisms of Panax ginseng action as an antidepressant. Cell Prolif. 2019, 52, e12696, doi:10.1111/cpr.12696.
  71. Lou, T.; Huang, Q.; Su, H.; Zhao, D.; Li, X. Targeting Sirtuin 1 signaling pathway by ginsenosides. J. Ethnopharmacol. 2020, 268, 113657, doi:10.1016/j.jep.2020.113657.
  72. Jiang, N.; Lv, J.; Wang, H.; Huang, H.; Wang, Q.; Lu, C.; Zeng, G.; Liu, X.M. Ginsenoside Rg1 ameliorates chronic social defeat stress-induced depressive-like behaviors and hippocampal neuroinflammation. Life Sci. 2020, 252, 117669, doi:10.1016/j.lfs.2020.117669.
  73. Fan, C.; Song, Q.; Wang, P.; Li, Y.; Yang, M.; Yu, S.Y. Neuroprotective Effects of Ginsenoside-Rg1 Against Depression-Like Behaviors via Suppressing Glial Activation, Synaptic Deficits, and Neuronal Apoptosis in Rats. Front. Immunol. 2018, 9, 2889, doi:10.3389/fimmu.2018.02889.
  74. Hu, J.F.; Song, X.Y.; Chu, S.F.; Chen, J.; Ji, H.J.; Chen, X.Y.; Yuan, Y.H.; Han, N.; Zhang, J.T.; Chen, N.H. Inhibitory effect of ginsenoside Rg1 on lipopolysaccharide-induced microglial activation in mice. Brain Res. 2011, 1374, 8–14, doi:10.1016/j.brainres.2010.11.069.
  75. Kaufmann, F.N.; Costa, A.P.; Ghisleni, G.; Diaz, A.P.; Rodrigues, A.L.S.; Peluffo, H.; Kaster, M.P. NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings. Brain Behav. Immun. 2017, 64, 367–383, doi:10.1016/j.bbi.2017.03.002.
  76. Arbore, G.; Kemper, C. A novel “complement-metabolism-inflammasome axis” as a key regulator of immune cell effector function. Eur. J. Immunol. 2016, 46, 1563–1573, doi:10.1002/eji.201546131.
  77. Walsh, J.G.; Muruve, D.A.; Power, C. Inflammasomes in the CNS. Nat. Rev. Neurosci. 2014, 15, 84–97, doi:10.1038/nrn3638.
  78. Shao, B.Z.; Cao, Q.; Liu, C. Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases. Front. Mol. Neurosci. 2018, 11, 320, doi:10.3389/fnmol.2018.00320.
  79. Alcocer-Gómez, E.; de Miguel, M.; Casas-Barquero, N.; Núñez-Vasco, J.; Sánchez-Alcazar, J.A.; Fernández-Rodríguez, A.; Cordero, M.D. NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav. Immun. 2014, 36, 111–117, doi:10.1016/j.bbi.2013.10.017.
  80. Zhang, Y.; Liu, L.; Liu, Y.Z.; Shen, X.L.; Wu, T.Y.; Zhang, T.; Wang, W.; Wang, Y.X.; Jiang, C.L. NLRP3 Inflammasome Mediates Chronic Mild Stress-Induced Depression in Mice via Neuroinflammation. Int. J. Neuropsychopharmacol. 2015, 18, pyv006, doi:10.1093/ijnp/pyv006.
  81. Zhang, Y.; Liu, L.; Peng, Y.L.; Liu, Y.Z.; Wu, T.Y.; Shen, X.L.; Zhou, J.R.; Sun, D.Y.; Huang, A.J.; Wang, X.; et al. Involvement of inflammasome activation in lipopolysaccharide-induced mice depressive-like behaviors. CNS Neurosci. Ther. 2014, 20, 119–124, doi:10.1111/cns.12170.
  82. Fu, Y.; Yang, P.; Zhao, Y.; Zhang, L.; Zhang, Z.; Dong, X.; Wu, Z.; Xu, Y.; Chen, Y. trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation. Evid. Based Complement. Alternat. Med. 2017, 2017, 4730878, doi:10.1155/2017/4730878.
  83. Liu, B.; Xu, C.; Wu, X.; Liu, F.; Du, Y.; Sun, J.; Tao, J.; Dong, J. Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation. Neuroscience 2015, 294, 193–205, doi:10.1016/j.neuroscience.2015.02.053.
  84. Nair, A.B.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 2016, 7, 27–31, doi:10.4103/0976-0105.177703.
  85. Juruena, M.F. Early-Life stress and HPA axis trigger recurrent adulthood depression. Epilepsy Behav. 2014, 38, 148–159, doi:10.1016/j.yebeh.2013.10.020.
  86. Juruena, M.F.; Agustini, B.; Cleare, A.J.; Young, A.H. A translational approach to clinical practice via stress-responsive glu-cocorticoid receptor signaling. Stem Cell Investig. 2017, 4, 13, doi:10.21037/sci.2017.02.01.
  87. Pandey, G.N.; Rizavi, H.S.; Bhaumik, R.; Ren, X. Increased protein and mRNA expression of corticotropin-releasing factor (CRF), decreased CRF receptors and CRF binding protein in specific postmortem brain areas of teenage suicide subjects. Psy-choneuroendocrinology 2019, 106, 233–243, doi:10.1016/j.psyneuen.2019.04.015.
  88. Horchar, M.J.; Wohleb, E.S. Glucocorticoid receptor antagonism prevents microglia-mediated neuronal remodeling and be-havioral despair following chronic unpredictable stress. Brain Behav. Immun. 2019, 81, 329–340, doi:10.1016/j.bbi.2019.06.030.
  89. Pariante, C.M.; Lightman, S.L. The HPA axis in major depression: Classical theories and new developments. Trends Neurosci. 2008, 31, 464–468, doi:10.1016/j.tins.2008.06.006.
  90. Gillespie, C.F.; Nemeroff, C.B. Hypercortisolemia and depression. Psychosom. Med. 2005, 67, S26–S28, doi:10.1097/01.psy.0000163456.22154.d2.
  91. D’Alessio, L.; Mesarosova, L.; Anink, J.J.; Kochen, S.; Solis, P.; Oddo, S.; Konopka, H.; Lyer, A.M.; Mühlebner, A.; Lucassen, P.J.; et al. Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug-resistant temporal lobe ep-ilepsy and comorbid depression. Epilepsia 2020, 61, 1595–1605, doi:10.1111/epi.16598.
  92. Yang, X.H.; Song, S.Q.; Xu, Y. Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats. Neuropsychiatr. Dis. Treat. 2017, 13, 2727–2736, doi:10.2147/NDT.S150028.
  93. Li, H.Y.; Zhao, Y.H.; Zeng, M.J.; Fang, F.; Li, M.; Qin, T.T.; Ye, L.Y.; Li, H.W.; Qu, R.; Ma, S.P. Saikosaponin D relieves un-predictable chronic mild stress induced depressive-like behavior in rats: Involvement of HPA axis and hippocampal neuro-genesis. Psychopharmacology 2017, 234, 3385–3394, doi:10.1007/s00213-017-4720-8.
  94. Pariante, C.M.; Lightman, S.L. The HPA axis in major depression: Classical theories and new developments. Trends Neurosci. 2008, 31, 464–468, doi:10.1016/j.tins.2008.06.006.
  95. Gillespie, C.F.; Nemeroff, C.B. Hypercortisolemia and depression. Psychosom. Med. 2005, 67, S26–S28, doi:10.1097/01.psy.0000163456.22154.d2.
  96. D’Alessio, L.; Mesarosova, L.; Anink, J.J.; Kochen, S.; Solis, P.; Oddo, S.; Konopka, H.; Lyer, A.M.; Mühlebner, A.; Lucassen, P.J.; et al. Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug-resistant temporal lobe ep-ilepsy and comorbid depression. Epilepsia 2020, 61, 1595–1605, doi:10.1111/epi.16598.
  97. Waters, R.P.; Rivalan, M.; Bangasser, D.A.; Deussing, J.M.; Ising, M.; Wood, S.K.; Holsboer, F.; Summers, C.H. Evidence for the role of corticotropin-releasing factor in major depressive disorder. Neurosci. Biobehav. Rev. 2015, 58, 63–78, doi:10.1016/j.neubiorev.2015.07.011.
  98. Fahmy, H.; Kuppast, B.; Ismail, M.T. Structure and Function of Small Non-Peptide CRF Antagonists and Their Potential Clinical Use. Curr. Mol. Pharmacol. 2017, 10, 270–281, doi:10.2174/1874467209666161101144155.
  99. Bhutada, P.; Mundhada, Y.; Bansod, K.; Ubgade, A.; Quazi, M.; Umathe, S.; Mundhada, D. Reversal by quercetin of cortico-trophin releasing factor induced anxiety- and depression-like effect in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 2010, 34, 955–960, doi:10.1016/j.pnpbp.2010.04.025.
  100. 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, 374–380, doi:10.1016/j.jnutbio.2009.01.008.
  101. Ketchesin, K.D.; Stinnett, G.S.; Seasholtz, A.F. Corticotropin-Releasing hormone-binding protein and stress: From invertebrates to humans. Stress 2017, 20, 449–464, doi:10.1080/10253890.2017.1322575.
  102. Nielsen, D.M. Corticotropin-Releasing factor type-1 receptor antagonists: The next class of antidepressants? Life Sci. 2006, 78, 909–919, doi:10.1016/j.lfs.2005.06.003.
  103. Henckens, M.J.; Deussing, J.M.; Chen, A. Region-Specific roles of the corticotropin-releasing factor-urocortin system in stress. Nat. Rev. Neurosci. 2016, 17, 636–651, doi:10.1038/nrn.2016.94.
  104. Im, E. Multi-Facets of Corticotropin-Releasing Factor in Modulating Inflammation and Angiogenesis. J. Neurogastroenterol. Motil. 2015, 21, 25–32, doi:10.5056/jnm14076.
  105. Dedic, N.; Chen, A.; Deussing, J.M. The CRF Family of Neuropeptides and their Receptors—Mediators of the Central Stress Response. Curr. Mol. Pharmacol. 2018, 11, 4–31, doi:10.2174/1874467210666170302104053.
  106. Paez-Pereda, M.; Hausch, F.; Holsboer, F. Corticotropin releasing factor receptor antagonists for major depressive disorder. Expert Opin. Investig. Drugs 2011, 20, 519–535, doi:10.1517/13543784.2011.565330.
  107. Menke, A. Is the HPA Axis as Target for Depression Outdated, or Is There a New Hope? Front. Psychiatry 2019, 10, 101, doi:10.3389/fpsyt.2019.00101.
  108. Jutkiewicz, E.M.; Wood, S.K.; Houshyar, H.; Hsin, L.W.; Rice, K.C.; Woods, J.H. The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats. Psychopharmacology 2005, 180, 215–223, doi:10.1007/s00213-005-2164-z.
  109. Thiagarajah, A.S.; Eades, L.E.; Thomas, P.R.; Guymer, E.K.; Morand, E.F.; Clarke, D.M.; Leech, M. GILZ: Glitzing up our un-derstanding of the glucocorticoid receptor in psychopathology. Brain Res. 2014, 1574, 60–69, doi:10.1016/j.brainres.2014.06.008.
  110. Simmen, U.; Bobirnac, I.; Ullmer, C.; Lübbert, H.; Berger Büter, K.; Schaffner, W.; Schoeffter, P. Antagonist effect of pseudo-hypericin at CRF1 receptors. Eur. J. Pharmacol. 2003, 458, 251–256, doi:10.1016/s0014-2999(02)02818-2.
  111. Thiagarajah, A.S.; Eades, L.E.; Thomas, P.R.; Guymer, E.K.; Morand, E.F.; Clarke, D.M.; Leech, M. GILZ: Glitzing up our un-derstanding of the glucocorticoid receptor in psychopathology. Brain Res. 2014, 1574, 60–69, doi:10.1016/j.brainres.2014.06.008.
  112. Leistner, C.; Menke, A. How to measure glucocorticoid receptor’s sensitivity in patients with stress-related psychiatric disorders. Psychoneuroendocrinology 2018, 91, 235–260, doi:10.1016/j.psyneuen.2018.01.023.
  113. Moraitis, A.G.; Block, T.; Nguyen, D.; Belanoff, J.K. The role of glucocorticoid receptors in metabolic syndrome and psychiatric illness. J. Steroid Biochem. Mol. Biol. 2017, 165, 114–120, doi:10.1016/j.jsbmb.2016.03.023.
  114. Sarubin, N.; Hilbert, S.; Naumann, F.; Zill, P.; Wimmer, A.M.; Nothdurfter, C.; Rupprecht, R.; Baghai, T.C.; Bühner,M.; Schüle, C. The sex-dependent role of the glucocorticoid receptor in depression: Variations in the NR3C1 gene are associated with major depressive disorder in women but not in men. Eur. Arch. Psychiatry Clin. Neurosci. 2017, 267, 123–133, doi:10.1007/s00406-016-0722-5.
  115. Pandey, G.N.; Rizavi, H.S.; Ren, X.; Dwivedi, Y.; Palkovits, M. Region-Specific alterations in glucocorticoid receptor expression in the postmortem brain of teenage suicide victims. Psychoneuroendocrinology 2013, 38, 2628–2639, doi:10.1016/j.psyneuen.2013.06.020.
  116. Guidotti, G.; Calabrese, F.; Anacker, C.; Racagni, G.; Pariante, C.M.; Riva, M.A. Glucocorticoid receptor and FKBP5 expression is altered following exposure to chronic stress: Modulation by antidepressant treatment. Neuropsychopharmacology 2013, 38, 616–627, doi:10.1038/npp.2012.225.
  117. Van Rossum, E.F.; Binder, E.B.; Majer, M.; Koper, J.W.; Ising, M.; Modell, S.; Salyakina, D.; Lamberts, S.W.; Holsboer, F. Pol-ymorphisms of the glucocorticoid receptor gene and major depression. Biol. Psychiatry 2006, 59, 681–688, doi:10.1016/j.biopsych.2006.02.007.
  118. Block, T.S.; Kushner, H.; Kalin, N.; Nelson, C.; Belanoff, J.; Schatzberg, A. Combined Analysis of Mifepristone for Psychotic Depression: Plasma Levels Associated with Clinical Response. Biol. Psychiatry 2018, 84, 46–54, doi:10.1016/j.biopsych.2018.01.008.
  119. Soria, V.; Gonzalez-Rodriguez, A.; Huerta-Ramos, E.; Usall, J.; Cobo, J.; Bioque, M.; Barbero, J.D.; García-Rizo, C.; Tost, M.; Monreal, J.A.; et al. Targeting hypothalamic-pituitary-adrenal axis hormones and sex steroids for improving cognition in major mood disorders and schizophrenia: A systematic review and narrative synthesis. Psychoneuroendocrinology 2018, 93, 8–19, doi:10.1016/j.psyneuen.2018.04.012.
  120. Wang, W.; Liu, L.; Yang, X.; Gao, H.; Tang, Q.K.; Yin, L.Y.; Yin, X.Y.; Hao, J.R.; Geng, D.Q.; Gao, C. Ketamine improved de-pressive-like behaviors via hippocampal glucocorticoid receptor in chronic stress induced-susceptible mice. Behav. Brain Res. 2019, 364, 75–84, doi:10.1016/j.bbr.2019.01.057.
  121. Garde, D. Corcept Tanks as Depression Drug Comes Up Short In Phase III. Available online: https://www.fiercebiotech.com/biotech/corcept-tanks-as-depression-drug-comes-up-short-phase-iii (accessed on May 5, 2014.).
  122. Clark, R.D. Glucocorticoid receptor antagonists. Curr. Top. Med. Chem. 2008, 8, 813–838, doi:10.2174/156802608784535011.
  123. Luo, Y.; Yang, M.; Guo, M.; Zhong, X.; Hu, Y. Huang Qin Hua Shi decoction for high-temperature- and high-humidity-induced cognitive-behavioral disorder in rats is associated with deactivation of the hypothalamic-pituitary-adrenal axis. J. Int. Med. Res. 2019, 47, 5752–5766, doi:10.1177/0300060519875369.
  124. Luo, Y.; Yang, M.; Guo, M.; Zhong, X.; Hu, Y. Huang Qin Hua Shi decoction for high-temperature- and high-humidity-induced cognitive-behavioral disorder in rats is associated with deactivation of the hypothalamic-pituitary-adrenal axis. J. Int. Med. Res. 2019, 47, 5752–5766, doi:10.1177/0300060519875369.
  125. Horowitz, M.A.; Cattaneo, A.; Cattane, N.; Lopizzo, N.; Tojo, L.; Bakunina, N.; Musaelyan, K.; Borsini, A.; Zunszain, P.A.; Pariante, C.M. Glucocorticoids prime the inflammatory response of human hippocampal cells through up-regulation of in-flammatory pathways. Brain Behav. Immun. 2020, 87, 777–794, doi:10.1016/j.bbi.2020.03.012.
  126. Bottasso, E. Toward the Existence of a Sympathetic Neuroplasticity Adaptive Mechanism Influencing the Immune Response. A Hypothetical View-Part II. Front. Endocrinol. 2019, 10, 633, doi:10.3389/fendo.2019.00633.
  127. Dai, S.; Mo, Y.; Wang, Y.; Xiang, B.; Liao, Q.; Zhou, M.; Li, X.; Li, Y.; Xiong, W.; Li, G.; et al. Chronic Stress Promotes Cancer Development. Front. Oncol. 2020, 10, 1492, doi:10.3389/fonc.2020.01492.
  128. Chrousos, G.P.; Gold, P.W. The concepts of stress and stress system disorders. Overview of physical and behavioral homeo-stasis. J. Am Med. Assoc. 1992, 267, 1244–1252, doi:10.1001/jama.1992.03480090092034.
  129. Chrousos, G.P. Stress and disorders of the stress system. Nat. Rev. Endocrinol. 2009, 5, 374–381, doi:10.1038/nrendo.2009.106.
  130. Bellavance, M.A.; Rivest, S. The HPA—Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain. Front. Immunol. 2014, 5, 136, doi:10.3389/fimmu.2014.00136.
  131. Dantzer, R. Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa. Physiol. Rev. 2018, 98, 477–504, doi:10.1152/physrev.00039.2016.
  132. Newton, R.; Holden, N.S. Separating transrepression and transactivation: A distressing divorce for the glucocorticoid receptor? Mol. Pharmacol. 2007, 72, 799–809, doi:10.1124/mol.107.038794.
  133. De Bosscher, K.; Vanden Berghe, W.; Haegeman, G. The interplay between the glucocorticoid receptor and nuclear factor-κB or activator protein-1: Molecular mechanisms for gene repression. Endocr. Rev. 2003, 24, 488–522, doi:10.1210/er.2002-0006.
  134. Bekhbat, M.; Rowson, S.A.; Neigh, G.N. Checks and balances: The glucocorticoid receptor and NFκB in good times and bad. Front. Neuroendocrinol. 2017, 46, 15–31, doi:10.1016/j.yfrne.2017.05.001.
  135. Wang, D.; Lin, W.; Pan, Y.; Kuang, X.; Qi, X.; Sun, H. Chronic blockade of glucocorticoid receptors by RU486 enhances lipo-polysaccharide-induced depressive-like behaviour and cytokine production in rats. Brain Behav. Immun. 2011, 25, 706–714, doi:10.1016/j.bbi.2011.01.011.
  136. Troubat, R.; Barone, P.; Leman, S.; Desmidt, T.; Cressant, A.; Atanasova, B.; Brizard, B.; Hage, W.E.; Surget, A.; Belzung, C.; et al. Neuroinflammation and depression: A review. Eur. J. Neurosci. 2020, doi:10.1111/ejn.14720.
  137. Li, K.D.; Yan, K.; Wang, Q.S.; Tian, J.S.; Xu, D.; Zhang, W.Y.; Cui, Y.L. Antidepressant-Like effects of dietary gardenia blue pigment derived from genipin and tyrosine. Food Funct. 2019, 10, 4533–4545, doi:10.1039/c9fo00480g.
  138. Dunn, A.J. Effects of cytokines and infections on brain neurochemistry. Clin. Neurosci. Res. 2006, 6, 52–68, doi:10.1016/j.cnr.2006.04.002.
  139. Chen, H.; Shi, H.; Liu, Y.; Ren, X.; He, S.; Chang, X.; Yin, Y. Activation of corticotropin-releasing factor receptor 1 aggravates dextran sodium sulphate-induced colitis in mice by promoting M1 macrophage polarization. Mol. Med. Rep. 2018, 17, 234–242, doi:10.3892/mmr.2017.7909.
  140. Knapp, D.J.; Whitman, B.A.; Wills, T.A.; Angel, R.A.; Overstreet, D.H.; Criswell, H.E.; Ming, Z.; Breese, G.R. Cytokine in-volvement in stress may depend on corticotrophin releasing factor to sensitize ethanol withdrawal anxiety. Brain Behav. Immun. 2011, 25, S146–S154, doi:10.1016/j.bbi.2011.02.018.
  141. Chatoo, M.; Li, Y.; Ma, Z.; Coote, J.; Du, J.; Chen, X. Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome. Front. Endocrinol. 2018, 9, 21, doi:10.3389/fendo.2018.00021.
  142. Frank, M.G.; Weber, M.D.; Watkins, L.R.; Maier, S.F. Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming. Brain Behav. Immun. 2015, 48, 1–7, doi:10.1016/j.bbi.2015.03.010.
  143. Alvarez-Carbonell, D.; Ye, F.; Ramanath, N.; Dobrowolski, C.; Karn, J. The Glucocorticoid Receptor Is a Critical Regulator of HIV Latency in Human Microglial Cells. J. Neuroimmune Pharmacol. 2019, 14, 94–109, doi:10.1007/s11481-018-9798-1.
  144. Wang, W.; Ji, P.; Dow, K.E. Corticotropin-Releasing hormone induces proliferation and TNF-α release in cultured rat microglia via MAP kinase signalling pathways. J. Neurochem. 2003, 84, 189–195, doi:10.1046/j.1471-4159.2003.01544.x.
  145. Herrera, A.J.; Espinosa-Oliva, A.M.; Carrillo-Jimenez, A.; Oliva-Martin, M.J.; Garcia-Revilla, J.; Garcia-Quintanilla, A.; Pablos, R.M.; Venero, J.L. Relevance of chronic stress and the two faces of microglia in Parkinson’s disease. Front. Cell. Neurosci. 2015, 9, 312, doi:10.3389/fncel.2015.00312.
  146. Kato, T.A.; Hayakawa, K.; Monji, A.; Kanba, S. Missing and Possible Link between Neuroendocrine Factors, Neuropsychiatric Disorders, and Microglia. Front. Integr. Neurosci. 2013, 7, 53, doi:10.3389/fnint.2013.00053.
  147. Raison, C.L.; Borisov, A.S.; Woolwine, B.J.; Massung, B.; Vogt, G.; Miller, A.H. Interferon-α effects on diurnal hypothalam-ic-pituitary-adrenal axis activity: Relationship with proinflammatory cytokines and behavior. Mol. Psychiatry 2010, 15, 535–547, doi:10.1038/mp.2008.58.
  148. Panossian, A.; Seo, E.J.; Efferth, T. Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology. Phytomedicine 2018, 50, 257–284, doi:10.1016/j.phymed.2018.09.204.
  149. Panossian, A.G.; Efferth, T.; Shikov, A.N.; Pozharitskaya, O.N.; Kuchta, K.; Mukherjee, P.K.; Banerjee, S.; Heinrich, M.; Wu, W.; Guo, D.A.; et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases. Med. Res. Rev. 2021, 41, 630–703, doi:10.1002/med.21743.
  150. Amsterdam, J.D.; Panossian, A.G. Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine 2016, 23, 770–783, doi:10.1016/j.phymed.2016.02.009.
  151. Fu, H.; Xu, Z.; Zhang, X.L.; Zheng, G.Q. Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer’s Disease and Depression: A Preclinical Systematic Review. Front. Neurosci. 2019, 13, 1421, doi:10.3389/fnins.2019.01421.
  152. Hu, Y.; Liu, X.; Zhang, T.; Chen, C.; Dong, X.; Can, Y.; Liu, P. Behavioral and Biochemical Effects of KXS on Postmyocardial Infarction Depression. Front. Pharmacol. 2020, 11, 561817, doi:10.3389/fphar.2020.561817.
  153. Dang, H.; Sun, L.; Liu, X.; Peng, B.; Wang, Q.; Jia, W.; Chen, Y.; Pan, A.; Xiao, P. Preventive action of Kai Xin San aqueous extract on depressive-like symptoms and cognition deficit induced by chronic mild stress. Exp. Biol. Med. 2009, 234, 785–793, doi:10.3181/0812-RM-354.
  154. Li, Y.; Wang, L.; Wang, P.; Fan, C.; Zhang, P.; Shen, J.; Yu, S.Y. Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats. Oxid. Med. Cell. Longev. 2020, 2020, 2325391, doi:10.1155/2020/2325391.
  155. Lee, K.J.; Ji, G.E. The effect of fermented red ginseng on depression is mediated by lipids. Nutr. Neurosci. 2014, 17, 7–15, doi:10.1179/1476830513y.0000000059.
  156. Lee, Y.Y.; Park, J.S.; Lee, E.J.; Lee, S.Y.; Kim, D.H.; Kang, J.L.; Kim, H.S. Anti-Inflammatory mechanism of ginseng saponin metabolite Rh3 in lipopolysaccharide-stimulated microglia: Critical role of 5′-adenosine monophosphate-activated protein kinase signaling pathway. J. Agric. Food Chem. 2015, 63, 3472–3480, doi:10.1021/jf506110y.
  157. Ke, L.; Guo, W.; Xu, J.; Zhang, G.; Wang, W.; Huang, W. Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage. Neural Regen. Res. 2014, 9, 252–259, doi:10.4103/1673-5374.128217.
  158. Chen, S.; Li, X.; Wang, Y.; Mu, P.; Chen, C.; Huang, P.; Liu, D. Ginsenoside Rb1 attenuates intestinal ische-mia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway. Mol. Med. Rep. 2019, 19, 3633–3641, doi:10.3892/mmr.2019.10018.
  159. Shi, Y.; Wang, H.; Zheng, M.; Xu, W.; Yang, Y.; Shi, F. Ginsenoside Rg3 suppresses the NLRP3 inflammasome activation through inhibition of its assembly. FASEB J. 2020, 34, 208–221, doi:10.1096/fj.201901537R.
  160. Lee, W.; Cho, S.H.; Kim, J.E.; Lee, C.; Lee, J.H.; Baek, M.C.; Song, G.Y.; Bae, J.S. Suppressive Effects of Ginsenoside Rh1 on HMGB1-Mediated Septic Responses. Am. J. Chin. Med. 2019, 47, 119–133, doi:10.1142/S0192415X1950006X.
  161. Kim, Y.; Lee, H.Y.; Choi, Y.J.; Cho, S.H. Antidepressant effects of ginsenoside Rf on behavioral change in the glial degeneration model of depression by reversing glial loss. J. Ginseng Res. 2020, 44, 603–610, doi:10.1016/j.jgr.2019.08.005.
  162. Li, Z.; Zhao, L.; Chen, J.; Liu, C.; Li, S.; Hua, M.; Qu, D.; Shao, Z.; Sun, Y. Ginsenoside Rk1 alleviates LPS-induced depres-sion-like behavior in mice by promoting BDNF and suppressing the neuroinflammatory response. Biochem. Biophys. Res. Commun. 2020, 530, 658–664, doi:10.1016/j.bbrc.2020.07.098.
  163. Zhang, Y.Q.; Wang, X.B.; Xue, R.R.; Gao, X.X.; Li, W. Ginsenoside Rg1 attenuates chronic unpredictable mild stress-induced depressive-like effect via regulating NF-κB/NLRP3 pathway in rats. Neuroreport 2019, 30, 893–900, doi:10.1097/WNR.0000000000001302.
  164. Hu, Y.; Liu, M.; Liu, P.; Guo, D.H.; Wei, R.B.; Rahman, K. Possible mechanism of the antidepressant effect of 3,6′-disinapoyl sucrose from Polygala tenuifolia Willd. J. Pharm. Pharmacol. 2011, 63, 869–874, doi:10.1111/j.2042-7158.2011.01281.x.
  165. Hu, Y.; Liu, P.; Guo, D.H.; Rahman, K.; Wang, D.X.; Xie, T.T. Antidepressant effects of the extract YZ-50 from Polygala tenuifolia in chronic mild stress treated rats and its possible mechanisms. Pharm. Biol. 2010, 48, 794–800, doi:10.3109/13880200903280034.
  166. Liu, P.; Hu, Y.; Guo, D.H.; Wang, D.X.; Tu, H.H.; Ma, L.; Xie, T.T.; Kong, L.Y. Potential antidepressant properties of Radix Polygalae (Yuan Zhi). Phytomedicine 2010, 17, 794–799, doi:10.1016/j.phymed.2010.01.004.
  167. Lee, S.R.; Lee, S.; Moon, E.; Park, H.J.; Park, H.B.; Kim, K.H. Bioactivity-Guided isolation of anti-inflammatory triterpenoids from the sclerotia of Poria cocos using LPS-stimulated Raw264.7 cells. Bioorg. Chem. 2017, 70, 94–99, doi:10.1016/j.bioorg.2016.11.012.
  168. Chang, W.; Teng, J. β-asarone prevents Aβ25-35-induced inflammatory responses and autophagy in SH-SY5Y cells: Down expression Beclin-1, LC3B and up expression Bcl-2. Int. J. Clin. Exp. Med. 2015, 8, 20658–20663.
  169. Chen, C.; Hu, Y.; Dong, X.Z.; Zhou, X.J.; Mu, L.H.; Liu, P. Proteomic Analysis of the Antidepressant Effects of Shen-Zhi-Ling in Depressed Patients: Identification of Proteins Associated with Platelet Activation and Lipid Metabolism. Cell. Mol. Neurobiol. 2018, 38, 1123–1135, doi:10.1007/s10571-018-0582-9.
  170. Dong, X.Z.; Wang, D.X.; Zhang, T.Y.; Liu, X.; Liu, P.; Hu, Y. Identification of protein targets for the antidepressant effects of Kai-Xin-San in Chinese medicine using isobaric tags for relative and absolute quantitation. Neural Regen. Res. 2020, 15, 302–310, doi:10.4103/1673-5374.265555.
  171. Zhao, S.; Iyengar, R. Systems pharmacology: Network analysis to identify multiscale mechanisms of drug action. Annu. Rev. Pharmacol. Toxicol. 2012, 52, 505–521, doi:10.1146/annurev-pharmtox-010611-134520.
  172. Woo, H.I.; Lim, S.W.; Myung, W.; Kim, D.K.; Lee, S.Y. Differentially expressed genes related to major depressive disorder and antidepressant response: Genome-Wide gene expression analysis. Exp. Mol. Med. 2018, 50, 92, doi:10.1038/s12276-018-0123-0.
  173. Panossian, A.; Hamm, R.; Wikman, G.; Efferth, T. Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: An interactive pathway analysis of the downstream effects using RNA microarray data. Phytomedicine 2014, 21, 1325–1348, doi:10.1016/j.phymed.2014.07.008.
  174. Panossian, A.; Seo, E.J.; Wikman, G.; Efferth, T. Synergy assessment of fixed combinations of Herba Andrographidis and Radix Eleutherococci extracts by transcriptome-wide microarray profiling. Phytomedicine 2015, 22, 981–992, doi:10.1016/j.phymed.2015.08.004.
  175. Panossian, A.; Seo, E.-J.; Efferth, T. Synergy assessments of plant extracts used in the treatment of stress and aging-related disorders. Synergy 2018, 7, 39–48, doi:10.1016/j.synres.2018.10.001.
  176. Panossian, A.; Hamm, R.; Kadioglu, O.; Wikman, G.; Efferth, T. Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells. Front. Neurosci. 2013, 7, 16, doi:10.3389/fnins.2013.00016.
  177. Wang, B.; Lu, S.; Zhang, C.; Zhu, L.; Li, Y.; Bai, M.; Xu, E. Quantitative proteomic analysis of the liver reveals antidepressant potential protein targets of Sinisan in a mouse CUMS model of depression. Biomed. Pharmacother. 2020, 130, 110565, doi:10.1016/j.biopha.2020.110565.
More