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Original Article | Open Access

Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression, elucidating the curative mechanism of Danzhi Xiaoyao powder

Kunyu Lia,1Leiming Youa,1Jianhua ZhenaGuangrui HuangaTing WangaYanan CaiaYunan ZhangaAnlong Xua,b( )
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China
School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China

1 These authors have contributed equally to this work.

Peer review under responsibility of Beijing University of Chinese Medicine.

Show Author Information

Abstract

Objective

To investigate the molecular mechanism and identify potential drugs for subthreshold depression (SD), and elucidate the detalied mechanism of Danzhi Xiaoyao powder (DZXY) in SD.

Methods

Using RNA-sequencing, we identified differentially expressed genes (DEGs) in leukocytes of SD compared to healthy controls, deciphered their functions and pathways, and identified the hub genes of SD. We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELiS platform. The Connectivity Map database was retrieved to screen candidate drugs for SD. Based on network pharmacology, we elucidated the “multi-component, multi-target, and multi-pathway” mechanism of DZXY in the treatment of SD.

Results

We identified 1080 DEGs (padj <0.05 and |log2 (fold change)| ≥ 1 & protein coding) in the leukocytes of patients with SD. These DEGs, including hub genes, were primarily involved in immune and inflammatory response-related processes. Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells. Connectivity Map analysis identified 28 potential drugs for SD treatment, particularly SB-202190 and TWS-119. Constructing the “Direct Compounds-Direct Targets-Pathways” network for DZXY and SD revealed the curative mechanisms of DZXY in SD, primarily including inflammatory response, lipid metabolism, immune response, and other processes.

Conclusion

These results provide new insights into the characteristics and functional changes of leukocytes in SD, partially illustrate the pathogenesis of SD, and suggest potential drugs for SD. The curative mechanisms of DZXY in SD are also partially elucidated.

References

1
Fu Xiaolan, Zhang Kai. Report on National Mental Health Development in China (2021-2022). Beijing, China: Social Sciences Academic Press; 2023.
2
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Arlington, USA: American Psychiatric Publishing; 2013.
3

Noyes BK, Munoz DP, Khalid-Khan S, Brietzke E, Booij L. Is subthreshold depression in adolescence clinically relevant? J Affect Disord. 2022;309:123-130.

4

Bakker GM. A new conception and subsequent taxonomy of clinical psychological problems. BMC Psychol. 2019;7(1):46.

5

Tuithof M, Ten Have M, Van Dorsselaer S, et al. Course of subthreshold depression into a depressive disorder and its risk factors. J Affect Disord. 2018;241:206-215.

6

Bertha EA, Balázs J. Subthreshold depression in adolescence: a systematic review. Eur Child Adolesc Psychiatry. 2013;22(10):589-603.

7

Herrman H, Patel V, Kieling C, et al. Time for united action on depression: a lancet-world psychiatric association commission. Lancet. 2022;399(10328):957-1022.

8

Pariante CM. Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation. Eur Neuropsychopharmacol. 2017;27(6):554-559.

9

Cole SW. The Conserved transcriptional response to adversity. Curr Opin Behav Sci. 2019;28:31-37.

10

Snyder-Mackler N, Sanz J, Kohn JN, et al. Social status alters immune regulation and response to infection in macaques. Science. 2016;354(6315):1041-1045.

11

Levine ME, Crimmins EM, Weir DR, Cole SW. Contemporaneous social environment and the architecture of late-life gene expression profiles. Am J Epidemiol. 2017;186(5):503-509.

12

Simons RL, Lei MK, Beach SRH, et al. An index of the ratio of inflammatory to antiviral cell types mediates the effects of social adversity and age on chronic illness. Soc Sci Med. 2017;185:158-165.

13

National Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of China: Part One. Beijing, China: Medical Science and Technology Press; 2020 [Chinese].

14

Subramanian A, Narayan R, Corsello SM, et al. A next generation connectivity map: l1000 platform and the first 1 000 000 profiles. Cell. 2017;171(6):1437-1452.

15

Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;4(11):682-690.

16

Li X, Liu Z, Liao J, et al. Network pharmacology approaches for research of traditional Chinese medicines. Chin J Nat Med. 2023;21(5):323-332.

17

Sadek N, Bona J. Subsyndromal symptomatic depression: a new concept. Depress Anxiety. 2000;12(1):30-39.

18

Zhang JP, You MY, Zhangyi CZ, et al. Identify tools and diagnostic criteria of subthreshold depression. World Chin Med. 2019;14(6):1425-1428 [Chinese].

19

Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.

20

Dailey AL. Metabolomic bioinformatic analysis. Methods Mol Biol. 2017;1606:341-352.

21

Yu G, Wang LG, Han Y, He QY. Cluster Profiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284-287.

22

Cole SW, Yan W, Galic Z, Arevalo J, Zack JA. Expression-based monitoring of transcription factor activity: the TELiS database. Bioinformatics. 2005;21(6):803-810.

23

Cole SW. Human social genomics. PLoS Genet. 2014;10(8):e1004601.

24

Mellon SH, Wolkowitz OM, Schonemann MD, et al. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment. Transl Psychiatry. 2016;6(5):e821.

25

Szklarczyk D, Kirsch R, Koutrouli M, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51(D1):D638-D646.

26

Chin CH, Chen SH, Wu HH, et al. Cyto Hubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8 (S4):S11.

27

Su WX, Zhao Y, Wei YQ, et al. Exploring the pathogenesis of psoriasis complicated with atherosclerosis via microarray data analysis. Front Immunol. 2021;12:667690.

28

Samart K, Tuyishime P, Krishnan A, Ravi J. Reconciling multiple connectivity scores for drug repurposing. Briefings Bioinf. 2021;22(6):bbab161.

29

Jiang JC, Hu CW, McIntosh AM, Shah S. Investigating the potential anti-depressive mechanisms of statins: a transcriptomic and Mendelian randomization analysis. Transl Psychiatry. 2023;13(1):110.

30

Ru JL, Li P, Wang JN, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminf. 2014;6(1):13.

31

Huang L, Xie DL, Yu YR, et al. Tcmid 2.0: a comprehensive resource for TCM. Nucleic Acids Res. 2018;46(D1):D1117-D1120.

32

Bindea G, Mlecnik B, Hackl H, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091-1093.

33

Bindea G, Galon J, Mlecnik B. CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics. 2013;29(5):661-663.

34

Tian CC, Tang XL, Zhu XY, et al. Expression profiles of circRNAs and the potential diagnostic value of serum circMARK3 in human acute Stanford type A aortic dissection. PLoS One. 2019;14(6):e0219013.

35

Jiang YX, Han DX, Zhao YF, et al. Multi-omics analysis of the prognosis and biological function for TRPV channel family in clear cell renal cell carcinoma. Front Immunol. 2022;13:872170.

36

Ayuso-Mateos JL, Nuevo R, Verdes E, Naidoo N, Chatterji S. From depressive symptoms to depressive disorders: the relevance of thresholds. Br J Psychiatry. 2010;196(5):365-371.

37

Crockett MA, Martínez V, Jiménez-Molina Á. Subthreshold depression in adolescence: gender differences in prevalence, clinical features, and associated factors. J Affect Disord. 2020;272:269-276.

38

Nicoloro-SantaBarbara JM, Carroll JE, Minissian M, et al. Immune transcriptional profiles in mothers with clinically elevated depression and anxiety symptoms several years post-delivery. Am J Reprod Immunol. 2022;88(5):e13619.

39

Slavich GM, Cole SW. The emerging field of human social genomics. Clin Psychol Sci. 2013;1(3):331-348.

40

Cole SW, Hawkley LC, Arevalo JM, et al. Social regulation of gene expression in human leukocytes. Genome Biol. 2007;8(9):R189.

41

Weber MD, Godbout JP, Sheridan JF. Repeated social defeat, neuroinflammation, and behavior: monocytes carry the signal. Neuropsychopharmacology. 2017;42(1):46-61.

42

Anacker C, Zunszain PA, Carvalho LA, Pariante CM. The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology. 2011;36(3):415-425.

43

Cho JH, Irwin MR, Eisenberger NI, Lamkin DM, Cole SW. Transcriptomic predictors of inflammation-induced depressed mood. Neuropsychopharmacology. 2019;44(5):923-929.

44

Saeed SA, Cunningham K, Bloch RM. Depression and anxiety disorders: benefits of exercise, yoga, and meditation. Am Fam Physician. 2019;99(10):620-627.

45

Wang GY, Liang C, Sun GJ. Yoga's therapeutic effect on perinatal depression: a systematic review and meta-analysis. Psychiatr Danub. 2022;34(2):195-204.

46

Sani NA, Yusoff SSM, Norhayati MN, Zainudin AM. Tai Chi exercise for mental and physical well-being in patients with depressive symptoms: a systematic review and meta-analysis. Int J Environ Res Publ Health. 2023;20(4):2828.

47

Reangsing C, Punsuwun S, Schneider JK. Effects of mindfulness interventions on depressive symptoms in adolescents: a meta-analysis. Int J Nurs Stud. 2021;115:103848.

48

Walton KG, Wenuganen S, Cole SW. Transcendental meditation practitioners show reduced expression of the conserved transcriptional response to adversity. Brain Behav Immun Health. 2023;32:100672.

49

Holmes L, Chinaka C, Elmi H, et al. Implication of spiritual network support system in epigenomic modulation and health trajectory. Int J Environ Res Public Health. 2019;16(21):4123.

50

Debnath M, Berk M, Maes M. Translational evidence for the inflammatory response system (IRS)/compensatory immune response system (CIRS) and neuroprogression theory of major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2021;111:110343.

51

Wang HQ, Wang ZZ, Chen NH. The receptor hypothesis and the pathogenesis of depression: genetic bases and biological correlates. Pharmacol Res. 2021;167:105542.

52

Zuo CC, Cao H, Song Y, et al. Nrf2: an all-rounder in depression. Redox Biol. 2022;58:102522.

53

Zgorzynska E, Dziedzic B, Walczewska A. An overview of the Nrf2/ARE pathway and its role in neurodegenerative diseases. Int J Mol Sci. 2021;22(17):9592.

54

Rosales C, Uribe-Querol E. Phagocytosis: a fundamental process in immunity. BioMed Res Int. 2017;2017:9042851.

55

Gallin JI. Neutrophil specific granule deficiency. Annu Rev Med. 1985;36:263-274.

56

Mitchell JP, Carmody RJ. NF-κB and the transcriptional control of inflammation. Int Rev Cell Mol Biol. 2018;335:41-84.

57

Caviedes A, Lafourcade C, Soto C, Wyneken U. BDNF/NF-κB signaling in the neurobiology of depression. Curr Pharmaceut Des. 2017;23(21):3154-3163.

58

Rodrigues FTS, De Souza MRM, Lima CNC, et al. Major depression model induced by repeated and intermittent lipopolysaccharide administration: long-lasting behavioral, neuroimmune and neuroprogressive alterations. J Psychiatr Res. 2018;107:57-67.

59

Talmon M, Rossi S, Pastore A, et al. Vortioxetine exerts anti-inflammatory and immunomodulatory effects on human monocytes/macrophages. Br J Pharmacol. 2018;175(1):113-124.

60

Ciafrè S, Ferraguti G, Tirassa P, et al. Nerve growth factor in the psychiatric brain. Riv Psichiatr. 2020;55(1):4-15.

61

Minnone G, De Benedetti F, Bracci-Laudiero L. NGF and its receptors in the regulation of inflammatory response. Int J Mol Sci. 2017;18(5):1028.

62

Erbay LG, Karlıdağ R, Oruç M, Çiğremiş Y, Celbiş O. Association of BDNF/TrkB and NGF/TrkA levels in postmortem brain with major depression and suicide. Psychiatr Danub. 2021;33(4):491-498.

63

Shi YC, Luan D, Song RZ, Zhang ZJ. Value of peripheral neurotrophin levels for the diagnosis of depression and response to treatment: a systematic review and meta-analysis. Eur Neuropsychopharmacol. 2020;41:40-51.

64

Mondal AC, Fatima M. Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment. Int J Neurosci. 2019;129(3):283-296.

65

Skaper SD. Nerve growth factor: a neuroimmune crosstalk mediator for all seasons. Immunology. 2017;151(1):1-15.

66

Andrés CMC, Pérez de la Lastra JM, Juan CA, Plou FJ, Pérez-Lebeña E. The role of reactive species on innate immunity. Vaccines (Basel). 2022;10(10):1735.

67

Savina A, Amigorena S. Phagocytosis and antigen presentation in dendritic cells. Immunol Rev. 2007;219:143-156.

68

Somani A, Singh AK, Gupta B, et al. Oxidative and nitrosative stress in major depressive disorder: a case control study. Brain Sci. 2022;12(2):144.

69

Zhang XY, Yao JK. Oxidative stress and therapeutic implications in psychiatric disorders. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;46:197-199.

70

Marsden WN. Synaptic plasticity in depression: molecular, cellular and functional correlates. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;43:168-184.

71

Chowdhury MAR, An J, Jeong S. The pleiotropic face of CREB family transcription factors. Mol Cell. 2023;46(7):399-413.

72

Shaywitz AJ, Greenberg ME. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem. 1999;68:821-861.

73

Alboni S, Benatti C, Capone G, et al. Time-dependent effects of escitalopram on brain derived neurotrophic factor (BDNF) and neuroplasticity related targets in the central nervous system of rats. Eur J Pharmacol. 2010;643(2-3):180-187.

74

Laifenfeld D, Karry R, Grauer E, Klein E, Ben-Shachar D. ATF2, a member of the CREB/ATF family of transcription factors, in chronic stress and consequent to antidepressant treatment: animal models and human post-mortem brains. Neuropsychopharmacology. 2004;29(3):589-597.

75

Abdallah MS, Ramadan AN, Omara-Reda H, et al. Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder. CNS Neurosci Ther. 2021;27(12):1540-1548.

76

Pláteník J, Fišar Z, Buchal R, et al. GSK3β, CREB, and BDNF in peripheral blood of patients with Alzheimer's disease and depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;50:83-93.

77

Capitanio JP, Cole SW. Social instability and immunity in rhesus monkeys: the role of the sympathetic nervous system. Philos Trans R Soc Lond B Biol Sci. 2015;370(1669):20140104.

78

Zhang HG, Wang B, Yang Y, et al. Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis. Cell Res. 2022;32(10):897-913.

79

Mamdani F, Berlim MT, Beaulieu MM, et al. Gene expression biomarkers of response to citalopram treatment in major depressive disorder. Transl Psychiatry. 2011;1(6):e13.

80

Mostafavi S, Battle A, Zhu X, et al. Type Ⅰ interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing. Mol Psychiatry. 2014;19(12):1267-1274.

81

Udina M, Castellví P, Moreno-España J, et al. Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry. 2012;73(8):1128-1138.

82

Pawlowski T, Malyszczak K, Inglot M, et al. Alterations in the metabolism of tryptophan in patients with chronic hepatitis C six months after pegylated interferon-α 2a treatment. Psychoneuroendocrinology. 2018;97:1-7.

83

Bonaccorso S, Marino V, Puzella A, et al. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol. 2002;22(1):86-90.

84

Raison CL, Dantzer R, Kelley KW, et al. CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry. 2010;15(4):393-403.

85

Amasi-Hartoonian N, Sforzini L, Cattaneo A, Pariante CM. Cause or consequence? Understanding the role of cortisol in the increased inflammation observed in depression. Curr Opin Endocr Metab Res. 2022;24:100356.

86

Hasselmann H, Gamradt S, Taenzer A, et al. Pro-inflammatory monocyte phenotype and cell-specific steroid signaling alterations in unmedicated patients with major depressive disorder. Front Immunol. 2018;9:2693.

87

Ratman D, Vanden Berghe W, Dejager L, et al. How glucocorticoid receptors modulate the activity of other transcription factors: a scope beyond tethering. Mol Cell Endocrinol. 2013;380(1-2):41-54.

88

He F, Ru XL, Wen T. NRF2, a transcription factor for stress response and beyond. Int J Mol Sci. 2020;21(13):4777.

89

Subba R, Ahmad MH, Ghosh B, Mondal AC. Targeting NRF2 in type 2 diabetes mellitus and depression: efficacy of natural and synthetic compounds. Eur J Pharmacol. 2022;925:174993.

90

Dang RZ, Wang MY, Li XH, et al. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway. J Neuroinflammation. 2022;19(1):41.

91

Gonçalves VF, Mendes-Silva AP, Koyama E, et al. Increased levels of circulating cell-free mtDNA in plasma of late life depression subjects. J Psychiatr Res. 2021;139:25-29.

92

Bakunina N, Pariante CM, Zunszain PA. Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology. 2015;144(3):365-373.

93

Zhang GY, Xu SX, Yuan Z, Shen L. Weighted gene coexpression network analysis identifies specific modules and hub genes related to major depression. Neuropsychiatric Dis Treat. 2020;16:703-713.

94

Herbet M, Szumełda I, Piątkowska-Chmiel I, Gawrońska-Grzywacz M, Dudka J. Beneficial effects of combined administration of fluoxetine and mitochondria-targeted antioxidant at in behavioural and molecular studies in mice model of depression. Behav Brain Res. 2021;405:113185.

95

Powell ND, Sloan EK, Bailey MT, et al. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc Natl Acad Sci U S A. 2013;110(41):16574-16579.

96

Cole SW, Levine ME, Arevalo JM, Ma J, Weir DR, Crimmins EM. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity. Psychoneuroendocrinology. 2015;62:11-17.

97

Ma K, Zhang H, Baloch Z. Pathogenetic and therapeutic applications of Tumor Necrosis Factor-α (TNF-α) in major depressive disorder: a systematic review. Int J Mol Sci. 2016;17(5):733.

98

Liu CS, Adibfar A, Herrmann N, Gallagher D, Lanctôt KL. Evidence for inflammation-associated depression. Curr Top Behav Neurosci. 2017;31:3-30.

99

Cattaneo A, Gennarelli M, Uher R, et al. Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline 'predictors' and longitudinal targets. Neuropsychopharmacology. 2013;8(3):377-385.

100

Abbott R, Whear R, Nikolaou V, et al. Tumor necrosis factor-α inhibitor therapy in chronic physical illness: a systematic review and meta-analysis of the effect on depression and anxiety. J Psychosom Res. 2015;79(3):175-184.

101

Uzzan S, Azab AN. Anti-TNF-α compounds as a treatment for depression. Molecules. 2021;26(8):2368.

102

Harsanyi S, Kupcova I, Danisovic L, Klein M. Selected biomarkers of depression: what are the effects of cytokines and inflammation? Int J Mol Sci. 2022;24(1):578.

103

Sha Q, Madaj Z, Keaton S, et al. Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy. Transl Psychiatry. 2022;12(1):35.

104

García-García ML, Tovilla-Zárate CA, Villar-Soto M, et al. Fluoxetine modulates the pro-inflammatory process of IL-6, IL-1β and TNF-α levels in individuals with depression: a systematic review and meta-analysis. Psychiatr Res. 2022;307:114317.

105

Maes M, Song C, Yirmiya R. Targeting IL-1 in depression. Expert Opin Ther Targets. 2012;16(11):1097-1112.

106

Tsai SJ. Role of interleukin 8 in depression and other psychiatric disorders. Prog Neuro-Psychopharmacol Biol Psychiatry. 2021;106:110173.

107

Kruse JL, Olmstead R, Hellemann G, et al. Interleukin-8 and lower severity of depression in females, but not males, with treatment-resistant depression. J Psychiatr Res. 2021;140:350-356.

108

Trizzino M, Zucco A, Deliard S, et al. EGR1 is a gatekeeper of inflammatory enhancers in human macrophages. Sci Adv. 2021;7(3):eaaz8836.

109

Duclot F, Kabbaj M. The role of Early Growth Response 1 (EGR1) in brain plasticity and neuropsychiatric disorders. Front Behav Neurosci. 2017;11:35.

110

Sancho-Balsells A, Borràs-Pernas S, Brito V, et al. Cognitive and emotional symptoms induced by chronic stress are regulated by EGR1 in a subpopulation of hippocampal pyramidal ueurons. Int J Mol Sci. 2023;24(4):3833.

111

Papp M, Gruca P, Faron-Górecka A, Kusmider M, Willner P. Genomic screening of Wistar and Wistar-Kyoto rats exposed to chronic mild stress and deep brain stimulation of prefrontal cortex. Neuroscience. 2019;423:66-75.

112

Covington HE, Lobo MK, Maze I, et al. Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci. 2010;30(48):16082-16090.

113

Kerman IA, Bernard R, Bunney WE, et al. Evidence for transcriptional factor dysregulation in the dorsal raphe nucleus of patients with major depressive disorder. Front Neurosci. 2012;6:135.

114

Zou K, Zeng ZG. Role of early growth response 1 in inflammation-associated lung diseases. Am J Physiol Lung Cell Mol Physiol. 2023;325(2):L143-L154.

115

Haller V, Nahidino P, Forster M, Laufer SA. An updated patent review of p38 MAP kinase inhibitors (2014-2019). Expert Opin Ther Pat. 2020;30(6):453-466.

116

Davies SP, Reddy H, Caivano M, Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000;351(Pt 1):95-105.

117

Samuvel DJ, Jayanthi LD, Bhat NR, Ramamoorthy S. A role for p38 mitogen-activated protein kinase in the regulation of the serotonin transporter: evidence for distinct cellular mechanisms involved in transporter surface expression. J Neurosci. 2005;25(1):29-41.

118

Malynn S, Campos-Torres A, Moynagh P, Haase J. The pro-inflammatory cytokine TNF-α regulates the activity and expression of the serotonin transporter (SERT) in astrocytes. Neurochem Res. 2013;38(4):694-704.

119

Haase J, Brown E. Integrating the monoamine, neurotrophin and cytokine hypotheses of depression, a central role for the serotonin transporter? Pharmacol Ther. 2015;147:1-11.

120

Zhu CB, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology. 2006;31(10):2121-2131.

121

Costemale-Lacoste JF, Guilloux JP, Gaillard R. The role of GSK-3 in treatment-resistant depression and links with the pharmacological effects of lithium and ketamine: a review of the literature. Encephale. 2016;42(2):156-164.

122

King MK, Pardo M, Cheng Y, et al. Glycogen synthase kinase-3 inhibitors: rescuers of cognitive impairments. Pharmacol Ther. 2014;141(1):1-12.

123

Jope RS. Glycogen synthase kinase-3 in the etiology and treatment of mood disorders. Front Mol Neurosci. 2011;4:16.

124

Kandar CC, Sen D, Maity A. Anti-inflammatory potential of GSK-3 inhibitors. Curr Drug Targets. 2021;22(13):1464-1476.

125

Ebeid MA, Habib MZ, Mohamed AM, et al. Cognitive effects of the GSK-3 inhibitor lithium in LPS/chronic mild stress rat model of depression: hippocampal and cortical neuroinflammation and tauopathy. Neurotoxicology. 2021;83:77-88.

126

Thiruvengadam M, Venkidasamy B, Subramanian U, et al. Bioactive compounds in oxidative stress-mediated diseases: targeting the NRF2/ARE signaling pathway and epigenetic regulation. Antioxidants (Basel). 2021;10(12):1859.

127

Okamoto H, Voleti B, Banasr M, et al. Wnt2 expression and signaling is increased by different classes of antidepressant treatments. Biol Psychiatry. 2010;68(6):521-527.

128

Liu RJ, Fuchikami M, Dwyer JM, et al. GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine. Neuropsychopharmacology. 2013;38(11):2268-2277.

129

Griebel G, Stemmelin J, Lopez-Grancha M, et al. The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer's disease in rodents. Sci Rep. 2019;9(1):18045.

130

Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H. Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biol Psychiatry. 2004;55(8):781-784.

131

Song DG, Zhang XJ, Chen JM, et al. Wnt canonical pathway activator TWS119 drives microglial anti-inflammatory activation and facilitates neurological recovery following experimental stroke. J Neuroinflammation. 2019;16(1):256.

132

Jin AP, Li B, Li W, Xiao D. PHLPP2 downregulation protects cardiomyocytes against hypoxia-induced injury through reinforcing Nrf2/ARE antioxidant signaling. Chem Biol Interact. 2019;314:108848.

133

Wang W, Li MC, Wang YF, et al. GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats. Mol Neurobiol. 2016;53(10):7028-7036.

134

Gao LM, Yang LJ, Cui H. GSK-3β inhibitor TWS119 alleviates hypoxic-ischemic brain damage via a crosstalk with Wnt and Notch signaling pathways in neonatal rats. Brain Res. 2021;1768:147588.

135

Chen YQ, Zheng L, Aldarouish M, et al. Wnt pathway activator TWS119 enhances the proliferation and cytolytic activity of human γδT cells against colon cancer. Exp Cell Res. 2018;362(1):63-71.

136

Tang YY, Sheng SY, Lu CG, et al. Effects of glycogen synthase kinase-3β inhibitor TWS119 on proliferation and cytokine production of TILs from human lung cancer. J Immunother. 2018;41(7):319-328.

137

Serna-Rodríguez MF, Bernal-Vega S, De la Barquera JAO, Camacho-Morales A, Pérez-Maya AA. The role of damage associated molecular pattern molecules (DAMPs) and permeability of the blood-brain barrier in depression and neuroinflammation. J Neuroimmunol. 2022;371:577951.

138

Guo JJ, Chang L, Li CL, et al. SB203580 reverses memory deficits and depression-like behavior induced by microinjection of Aβ1-42 into hippocampus of mice. Metab Brain Dis. 2017;32(1):57-68.

139

Guo XY, Mao RZ, Cui LC, et al. PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomized placebo-controlled trial protocol. Gen Psychiatr. 2021;34(2):e100440.

140

Zhu X, Zhang YM, Zhang MY, Chen YJ, Liu YW. Hesperetin ameliorates diabetes-associated anxiety and depression-like behaviors in rats via activating Nrf2/ARE pathway. Metab Brain Dis. 2021;36(7):1969-1983.

141

Kumar AR, Kurup PA. Inhibition of membrane Na+-K+ ATPase activity: a common pathway in central nervous system disorders. J Assoc Phys India. 2002;50:400-406.

142

Kurup AR, Kurup PA. Membrane Na+-K+ ATPase mediated cascade in bipolar mood disorder, major depressive disorder, and schizophrenia, relationship to hemispheric dominance. Int J Neurosci. 2002;112(8):965-982.

143

Valvassori SS, Aguiar-Geraldo JM, Possamai-Della T, et al. Depressive-like behavior accompanies neuroinflammation in an animal model of bipolar disorder symptoms induced by ouabain. Pharmacol Biochem Behav. 2022;219:173434.

144

Goldstein I, Levy T, Galili D, et al. Involvement of Na+, K+-ATPase and endogenous digitalis-like compounds in depressive disorders. Biol Psychiatr. 2006;60(5):491-499.

145

Filho CB, Jesse CR, Donato F, et al. Chronic unpredictable mild stress decreases BDNF and NGF levels and Na+, K+-ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant effect of chrysin. Neuroscience. 2015;289:367-380.

146

Ren JN, Song D, Bai QF, Verkhratsky A, Peng L. Fluoxetine induces alkalinization of astroglial cytosol through stimulation of sodium-hydrogen exchanger 1: dissection of intracellular signaling pathways. Front Cell Neurosci. 2015;9:61.

147

Li J, Xu B, Chen Z, et al. PI3K/AKT/JNK/p38 signaling pathway-mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant-like effect of pioglitazone. Clin Exp Pharmacol Physiol. 2018;45(6):525-535.

148

Kawano T, Inokuchi J, Eto M, Murata M, Kang JH. Activators and inhibitors of Protein Kinase C (PKC): their applications in clinical trials. Pharmaceutics. 2021;13(11):1748.

149

Bagh MB, Maiti AK, Jana S, et al. Quinone and oxyradical scavenging properties of N-acetylcysteine prevent dopamine mediated inhibition of Na+, K+-ATPase and mitochondrial electron transport chain activity in rat brain: implications in the neuroprotective therapy of Parkinson's disease. Free Radic Res. 2008;42(6):574-581.

150

Salony, Solé X, Alves CP, et al. AKT inhibition promotes nonautonomous cancer cell survival. Mol Cancer Therapeut. 2016;15(1):142-153.

151

Vaccarino V, Brennan ML, Miller AH, et al. Association of major depressive disorder with serum myeloperoxidase and other markers of inflammation: a twin study. Biol Psychiatry. 2008;64(6):476-483.

152

Gałecki P, Gałecka E, Maes M, et al. The expression of genes encoding for COX-2, MPO, iNOS, and sPLA2-ⅡA in patients with recurrent depressive disorder. J Affect Disord. 2012;138(3):360-366.

153

Nobis A, Zalewski D, Waszkiewicz N. Peripheral markers of depression. J Clin Med. 2020;9(12):3793.

154

Blizniewska-Kowalska K, Gałecki P, Su KP, et al. Expression of PON1, PON2, PON3 and MPO genes in patients with depressive disorders. J Clin Med. 2022;11(12):3321.

155

Hao WZ, Wang L, Huang JQ, Chen JX. Research progress on the pharmacodynamic mechanism of antidepressant compound prescriptions and its flavonoids active ingredients. Acta Pharm Sin B. 2022;57(10):3035-3046 [Chinese].

156

Chen S, Tang YH, Gao Y, et al. Antidepressant potential of quercetin and its glycoside derivatives: a comprehensive review and update. Front Pharmacol. 2022;13:865376.

157

Wang YQ, Wang YH, Zou MS, et al. Research progress on antidepressant effect and mechanism of quercetin and its glycoside derivatives. Chin Tradit Herb Drugs. 2022;53(5):1548-1557 [Chinese].

158

Achour M, Ferdousi F, Sasaki K, Isoda H. Luteolin modulates neural stem cells fate determination: in vitro study on human neural stem cells, and in vivo study on LPS-induced depression mice model. Front Cell Dev Biol. 2021;9:753279.

159

Cheng Y, Wang XX, Yu YH, et al. Noise induced depression-like behavior, neuroinflammation and synaptic plasticity impairments: the protective effects of luteolin. Neurochem Res. 2022;47(11):3318-3330.

160

Chen L, Wang XK, Zhang YP, et al. Daidzein alleviates hypothalamic-pituitary-adrenal axis hyperactivity, ameliorates depression-Like behavior, and partly rectifies circulating cytokine imbalance in two rodent models of depression. Front Behav Neurosci. 2021;15:671864.

161

Gao LN, Yan MC, Zhou LR, et al. Puerarin alleviates depression-like behavior induced by high-fat diet combined with chronic unpredictable mild stress via repairing TLR4-induced inflammatory damages and phospholipid metabolism disorders. Front Pharmacol. 2021;12:767333.

162

Zhao J, Jia YZ, Zhao W, et al. Botanical drug puerarin ameliorates liposaccharide-induced depressive behaviors in mice via inhibiting Raga/mTOR/p70S6K pathways. Oxid Med Cell Longev. 2021;2021:7716201.

163

Li HY, Wang J, Liang LF, et al. Sirtuin 3 plays a critical role in the antidepressant- and anxiolytic-like effects of kaempferol. Antioxidants. 2022;11(10):1886.

164

Gao WQ, Wang W, Peng Y, Deng ZF. Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade. Metab Brain Dis. 2019;34(2):485-494.

165

Chen YK, Zeng A, Luo ZH, et al. Advances on pharmacology of β-sitosterol. J Guangdong Pharm Univ. 2021;37(1):148-153 [Chinese].

Journal of Traditional Chinese Medical Sciences
Pages 3-20
Cite this article:
Li K, You L, Zhen J, et al. Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression, elucidating the curative mechanism of Danzhi Xiaoyao powder. Journal of Traditional Chinese Medical Sciences, 2024, 11(1): 3-20. https://doi.org/10.1016/j.jtcms.2023.12.001

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Received: 06 November 2023
Revised: 03 December 2023
Accepted: 03 December 2023
Published: 04 December 2023
© 2024 Beijing University of Chinese Medicine.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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