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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 1: 22 - 31

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.01.003

Quantitative proteomic analysis of the brain reveals the potential antidepressant mechanism of Jiawei Danzhi Xiaoyao San (加味丹栀逍遥散) in a chronic unpredictable mild stress mouse model of depression

  • Yajing LI ,
  • Baoying WANG ,
  • Wenxue SHAO ,
  • Shuaifei LU ,
  • Pan SU ,
  • Ming BAI ,
  • Erping XU ,
  • Yucheng LI
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  • 1 Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan Province, Zhengzhou 450046, China
    2 Academy of Chinese Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China
    3 Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou 450046, China
    4 School of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China
    5 School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China

Received date: 2023-12-22

  Accepted date: 2024-04-15

  Online published: 2025-01-10

Supported by

the National Natural Science Foundation of China: Study on the Biological Basis of Jiawei Danzhi Xiaoyaosan in Treatment of Depression based on Network Pharmacology and Proteomics(81973739);Natural Science Excellent Youth Fund of Henan Province: the Mechanism of Baicalin Regulates the GSK3B-Mediated Axoplasmic Transport in the Treatment of Depression(202300410249);Science and Technology Research Project of Henan Province: Study on the Antidepressant Mechanism of Jiawei Danzhi Xiaoyaosan based on the NOD-like Receptor Thermal Protein Domain-associated Protein and Tripartite Motif-containing Protein 31 Ubiquitination Pathway(222102310233);Study on the Mechanism of Jiawei Danzhi Xiaoyaosan in the Treatment of Depression by Regulating M1/M2 Polarization and Microglia Autophagy(232102310419)

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Abstract

OBJECTIVE: To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan (加味丹栀逍遥散,JD) in chronic unpredictable mild stress (CUMS)-induced depression in mice.

METHODS: Using the CUMS mouse model of depression, the antidepressant effects of JD were assessed using the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Tandem mass tag (TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment. Hierarchical clustering, Gene Ontology function annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interactions (PPIs) were used to analyze differentially expressed proteins (DEPs), which were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.

RESULTS: Behavioral tests confirmed the anti-depressant effects of JD, and bioinformatics analysis revealed 59 DEPs, including 33 up-regulated and 26 down-regulated proteins, between the CUMS and JD-M groups. KEGG and PPI analyses revealed that neuro-filament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression. qRT-PCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light (NEFL) and medium (NEFM) and inhibited the phosphorylation of extracellular regulated kinase 1/2 (ERK1/2), whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM.

CONCLUSIONS: The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.

Key words： depression; proteomics; intermediate filaments; mitogen-activated protein kinases; Jiawei Danzhi Xiaoyaosan

Cite this article

Yajing LI , Baoying WANG , Wenxue SHAO , Shuaifei LU , Pan SU , Ming BAI , Erping XU , Yucheng LI . Quantitative proteomic analysis of the brain reveals the potential antidepressant mechanism of Jiawei Danzhi Xiaoyao San (加味丹栀逍遥散) in a chronic unpredictable mild stress mouse model of depression[J]. Journal of Traditional Chinese Medicine, 2025 , 45(1) : 22 -31 . DOI: 10.19852/j.cnki.jtcm.2025.01.003

References

1. K?nig H, K?nig HH, Konnopka A. The excess costs of depression: a systematic review and Meta-analysis. Epidemiol Psychiatr Sci 2019; 29: e30.
2. Huang Y, Wang Y, Wang H, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry 2019; 6: 211-24.
3. Marwaha S, Palmer E, Suppes T, et al. Novel and emerging treatments for major depression. Lancet 2023; 401: 141-53.
4. Voican CS, Corruble E, Naveau S, et al. Antidepressant-induced liver injury: a review for clinicians. Am J Psychiatry 2014; 171: 404-15.
5. Rothmore J. Antidepressant-induced sexual dysfunction. Med J Aust 2020; 212: 329-34.
6. Zhuang W, Liu SL, Xi SY, et al. Traditional Chinese Medicine decoctions and Chinese patent medicines for the treatment of depression: efficacies and mechanisms. J Ethnopharmacol 2023; 307: 116272.
7. Feng L, Xing H, Zhang K. The therapeutic potential of Traditional Chinese Medicine in depression: targeting adult hippocampal neurogenesis. Phytomedicine 2022; 98: 153980.
8. Ruan J, Chen S, Liang J, et al. Traditional Chinese Medicine-based integrated health interventions for depression: a systematic review and Meta-analysis. J Clin Nurs 2023; 32: 5632-51.
9. Xue Ji (Ming dynasty). Lei Ke Zhai Yao. Beijing: China Medical Science and Technology Publishing House, 2012: 12.
10. Wang XL, Feng ST, Wang YT, et al. Canonical Chinese medicine formula Danzhi-Xiaoyao-San for treating depression: a systematic review and Meta-analysis. J Ethnopharmacol 2022; 287: 114960.
11. Zhu X, Wu S, Zhou Y, et al. The pharmacological actions of Danzhi-xiaoyao-San on depression involve lysophosphatidic acid and microbiota-gut-brain axis: novel insights from a systems pharmacology analysis of a double-blind, randomized, placebo-controlled clinical trial. J Biomol Struct Dyn 2024;42: 9309-24.
12. Ding C, Xu M, Gao L, et al. Clinical efficacy of Danzhi Xiaoyao powder in the treatment of post-stroke depression: a protocol for randomized, double-blind clinical study. Medicine (Baltimore) 2021; 100: e27318.
13. Su R, Fan J, Li T, et al. Jiawei Xiaoyao capsule treatment for mild to moderate major depression with anxiety symptoms: a randomized, double-blind, double-dummy, controlled, multicenter, parallel-treatment trial. J Tradit Chin Med 2019; 39: 410-7.
14. Kou MJ, Chen JX. Integrated Traditional and Western Medicine for treatment of depression based on syndrome differentiation: a Meta-analysis of randomized controlled trials based on the Hamilton depression scale. J Tradit Chin Med 2012; 32: 1-5.
15. Tran DNH, Hwang IH, Chen FJ, et al. Core prescription pattern of Chinese herbal medicine for depressive disorders in Taiwan: a nationwide population-based study. Integr Med Res 2021; 10: 100707.
16. Su P, Wu M, Yin X, et al. Modified Xiaoyao San reverses lipopolysaccharide-induced depression-like behavior through suppressing microglia M1 polarization via enhancing autophagy involved in PI3K/Akt/mTOR pathway in mice. J Ethnopharmacol 2023; 315: 116659.
17. Tang XM, Guo JL, Chen L, et al. Application for proteomics analysis technology in studying animal-derived Traditional Chinese Medicine: a review. J Pharm Biomed Anal 2020; 191: 113609.
18. Willner P, Towell A, Sampson D, et al. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl) 1987; 93: 358-64.
19. Wi?niewski JR, Zougman A, Nagaraj N, et al. Universal sample preparation method for proteome analysis. Nat Methods 2009; 6: 359-62.
20. G?tz S, García-Gómez JM, Terol J, et al. High-throughput functional annotation and data mining with the Blast2GO suite. Nucleic Acids Res 2008; 36: 3420-35.
21. Kanehisa M, Goto S, Sato Y, et al. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res 2012; 40: D109-14.
22. Bomont P. The dazzling rise of neurofilaments: physiological functions and roles as biomarkers. Curr Opin Cell Biol 2021; 68: 181-91.
23. Bott CJ, Winckler B. Intermediate filaments in developing neurons: beyond structure. Cytoskeleton (Hoboken) 2020; 77: 110-28.
24. Thebault S, Booth RA, Freedman MS. Blood neurofilament light chain: the neurologist's troponin? Biomedicines 2020; 8: 523.
25. Gaetani L, Blennow K, Calabresi P, et al. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry 2019; 90: 870-81.
26. Liu Y, Tang X. Depressive syndromes in autoimmune disorders of the nervous system: prevalence, etiology, and influence. Front Psychiatry 2018; 9: 451.
27. Guedes VA, Kenney K, Shahim P, et al. Exosomal neurofilament light: a prognostic biomarker for remote symptoms after mild traumatic brain injury? Neurology 2020; 94: e2412-23.
28. Chen MH, Liu YL, Kuo HW, et al. Neurofilament light chain is a novel biomarker for major depression and related executive dysfunction. Int J Neuropsychopharmacol 2022; 25: 99-105.
29. Travica N, Berk M, Marx W. Neurofilament light protein as a biomarker in depression and cognitive function. Curr Opin Psychiatry 2022; 35: 30-7.
30. Maller JJ, Thomson RH, Lewis PM, et al. Traumatic brain injury, major depression, and diffusion tensor imaging: making connections. Brain Res Rev 2010; 64: 213-40.
31. Chen Y, Xie HQ, Sha R, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and up-regulation of neurofilament expression in neuronal cells: evaluation of AhR and MAPK pathways. Environ Int 2020; 134: 105193.
32. Wang JQ, Mao L. The ERK pathway: molecular mechanisms and treatment of depression. Mol Neurobiol 2019; 56: 6197-205.
33. Jia W, Liu R, Shi J, et al. Differential regulation of MAPK phosphorylation in the dorsal hippocampus in response to prolonged morphine withdrawal-induced depressive-like symptoms in mice. PLoS One 2013; 8: e66111.
34. Liu W, Ge T, Leng Y, et al. The role of neural plasticity in depression: from hippocampus to prefrontal cortex. Neural Plast 2017; 2017: 6871089.
35. Galeotti N, Ghelardini C. Regionally selective activation and differential regulation of ERK, JNK and p38 MAP kinase signalling pathway by protein kinase C in mood modulation. Int J Neuropsychopharmacol 2012; 15: 781-93.
36. Li X, Liu Z, Li W, et al. PTPRR regulates ERK dephosphorylation in depression mice model. J Affect Disord 2016; 193: 233-41.
37. Yao W, Cao Q, Luo S, et al. Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine. Mol Psychiatry 2022; 27: 1618-29.
38. Guan L, Jia N, Zhao X, et al. The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats. Brain Res Bull 2013; 99: 1-8.
39. Zentrich E, Han SY, Pessoa-Brandao L, et al. Collaboration of JNKs and ERKs in nerve growth factor regulation of the neurofilament light chain promoter in PC12 cells. J Biol Chem 2002; 277: 4110-8.
40. Han Q, Lin Q, Huang P, et al. Microglia-derived IL-1β contributes to axon development disorders and synaptic deficit through p38-MAPK signal pathway in septic neonatal rats. J Neuroinflammation 2017; 14: 52.
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