Original Articles

Metabolomics and network pharmacology analysis of mechanisms underlying amelioration of tic disorders in rats by Jiawei Huangan Lipi decoction (加味缓肝理脾汤)

  • CHEN Lijin ,
  • CHEN Linghui ,
  • WANG Chengrui ,
  • FANG Yijun ,
  • GAN Liping ,
  • HANG Jinyu
Expand
  • 1 Department of Pharmacy, Zhangzhou Traditional Chinese Medical Hospital, Zhangzhou 363000, China
    2 Department of Pediatrics, Zhangzhou Traditional Chinese Medical Hospital, Zhangzhou 363000, China
    3 School of Medicine and Health, Harbin Institute of Technology, Harbin150001, China; Zhengzhou Advanced Research Institute of Harbin Institute of Technology, Zhengzhou 450000, China
    4 Department of aircrew, General Hospital of Xinjiang Military Region, Urumqi 830000, China

Received date: 2025-05-28

  Accepted date: 2025-11-07

  Online published: 2026-08-08

Supported by

Fujian Natural Science Foundation: Mechanisms of Jiawei Huangan Lipi decoction in Treating Tic Disorders Investigated by Network Pharmacology and Metabolomics(2023J011851)

Abstract

OBJECTIVE: To further investigate the mechanism of Jiawei Huangan Lipi decoction (加味缓肝理脾汤, JHD) in treating tic disorders (TD) based on metabolomics and network pharmacology.

METHODS: The TD model rats were established using iminodipropionitrile and Shengdahuang (Radix Et Rhizoma Rhei Palmati) powder, combined with tail clamping and cold stimulation to induce pathology. Liquid chromatography-mass spectrometry (LC-MS) was used to analyse the chemical constituents of JHD, integrated network pharmacology to predict its therapeutic targets and pathways, and validated findings through reverse transcription quantitative polymerase chain reaction, Western blot and metabolomics. LC-MS-based serum metabolomics coupled with pattern recognition techniques identified endogenous differential metabolites and elucidated associated metabolic pathways.

RESULTS: Integrated metabolomics and network pharmacology revealed JHD's 744 compounds targeting 247 genes, notably ras-related C3 botulinum toxin substrate-alpha serine/threonine kinase 1, interleukin 6, tumor necrosis factor, estrogen receptor 1, interleukin-1β were highlighted, indicating that JHD may mitigate the incidence of TD by modulating these pivotal genes. The identified targets were predominantly enriched in pathways related to cancer, lipid metabolism and atherosclerosis, malaria, cAMP signaling, and neuroactive ligand-receptor interactions. Metabolomics identified 255 differential metabolites in TD, with JHD reversing 85 linked to linoleic acid, taurine, and biotin metabolism pathways. These pathways may underpin JHD's therapeutic effects against TD.

CONCLUSION: The study systematically explored JHD's mechanism by cross-integrating metabolomics-derived biomarker pathways with network pharmacology predictions, and it may be a useful alternative therapy for the treatment of TD.

Cite this article

CHEN Lijin , CHEN Linghui , WANG Chengrui , FANG Yijun , GAN Liping , HANG Jinyu . Metabolomics and network pharmacology analysis of mechanisms underlying amelioration of tic disorders in rats by Jiawei Huangan Lipi decoction (加味缓肝理脾汤)[J]. Journal of Traditional Chinese Medicine, 2026 , 46(4) : 916 -926 . DOI: 10.19852/j.cnki.jtcm.2026.04.012

References

1. Lu Q, Sun D, Liu ZS. Interpretation of expert consensus for diagnosis and treatment of tic disorders in China. Zhong Hua Ying Yong Lin Chuang Er Ke Za Zhi 2021; 36: 647-53.
2. Chen M, Tu Y, Yang HM. Cohort study on the influencing factor in tic disorders for children. Zhong Guo Shi Yong Shen Jing Bing Xue Za Zhi 2018; 21: 124-8.
3. Kong M, Yan SJ, Gao YN, Li H. Is traditional Chinese medicine effective in treating tic disorders (tourette syndrome) a Meta-analysis of randomized controlled trials. Complement Med Res 2023; 30: 248-57.
4. Wu Q (Qing dynasty). Yi Zong Jin Jian. Beijing: People's Medical Publishing House, 1973: 68.
5. Hang JY, Fang YJ, Han HY, Weng WT. 32 Cases of Jiawei Huangan Lipi decoction combined with Yijinjing in treating pediatric tic disorder with spleen deficiency and liver hyperactivity. Fujian Zhong Yi Za Zhi 2022; 53: 59-60+63.
6. Zhang ZY, Yi PJ, Yang JJ, et al. Integrated network pharmacology analysis and serum metabolomics to reveal the cognitive improvement effect of Bushen Tiansui formula on Alzheimer's disease. J Ethnopharmacol 2020; 249: 112371.
7. Zhang YL, Ma WG, Qian XY, et al. Construction of experimental animal models and evaluation of spleen deficiency syndrome: a review. Zhong Guo Shi Yan Dong Wu Xue Bao 2024; 32: 385-96.
8. Shi WL, Chen HM, Ma BX. Advances in establishment and application of tic disorder animal model with spleen deficiency and liver hyperactivity syndrome. Shi Jie Zhong Yi Yao 2022; 17: 3559-63.
9. Ke ZL, Chen YH. Research progress in animal models for tic disorder. Zhong Hua Shi Yong Er Ke Lin Chuan Za Zhi 2024; 39: 288-92.
10. Want EJ, O'Maille G, Smith CA, et al. Solvent-dependent metabolite distribution, clustering, and protein extraction for serum profiling with mass spectrometry. Anal Chem 2006; 78: 743-52.
11. Barri T, Dragsted LO. UPLC-ESI-QTOF/MS and multivariate data analysis for blood plasma and serum metabolomics: effect of experimental artefacts and anticoagulant. Anal Chim Acta 2013; 768: 118-28.
12. Ru JL, Li P, Wang JN, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6: 13.
13. Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017:quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 2017; 45: D362-8.
14. Burley SK, Berman HM, Kleywegt GJ, et al. Protein data bank (PDB): The single global macromolecular structure archive. Methods Mol Biol 2017; 1607: 627-41.
15. Chong J, Xia JG. MetaboAnalystR: an R package for flexible and reproducible analysis of metabolomics data. Bioinformatics 2018; 34: 4313-4.
16. Chen YG, Tu YQ, Wang CQ, Chen J, Zhang BH. Network pharmacology and molecular docking to discuss the mechanism of Jinhutongdan prescription in the treatment of cholelithiasis and experimental verification. Zhong Guo Lin Chuang Yu Zhi Liao Xue Za Zhi 2022; 27: 1090-8.
17. Cheng Y, Huang S, Feng YJ, Tang Y. Effects of zhichou decoction on tic behavior and TNF-α, IL-6, IL-1β of tic disorder model rats. Yunnan Zhong Yi Yao Da Xue Xue Bao 2021; 44: 17-21.
18. Ma BT, Wu M, Zhou YB, Zhang JM, Zhang X. Clinical practice guide of Traditional Chinese Medicine for child tic disorder treatment. Guo Ji Zhong Yi Zhong Yao Za Zhi 2012; 34: 1098-101.
19. Wang B, Wu LJ, Chen J, et al. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Signal Transduct Target Ther 2021; 6: 94.
20. Perez-Castro L, Garcia R, Venkateswaran N, Barnes S, Conacci-Sorrell M. Tryptophan and its metabolites in normal physiology and cancer etiology. Febs j 2023; 290: 7-27.
21. Jasani B, Simmer K, Patole SK, Rao SC. Long chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev 2017; 3: Cd000376.
22. Ghasemzadeh Rahbardar M, Razavi BM, Hosseinzadeh H. Investigating the ameliorative effect of alpha-mangostin on development and existing pain in a rat model of neuropathic pain. Phytother Res 2020; 34: 3211-25.
23. Wang J, Xian JM, Zhang RH, et al. α-mangostin exhibits antitumor activity against NCI-H1975 cells via the EGFR/STAT3 pathway: an experimental and molecular simulation study. Molecules. 2025; 30: 1294.
24. Deepika, Maurya PK. Health benefits of quercetin in age-related diseases. Molecules. 2022; 27: 2498.
25. Jin S, Zhang LJ, Wang L. Kaempferol, a potential neuroprotective agent in neurodegenerative diseases: from chemistry to medicine. Biomed Pharmacother 2023; 165: 115215.
26. Li ZB, Zheng Y, Liu K, et al. Lignans as multi-targeted natural products in neurodegenerative diseases and depression: recent perspectives. Phytother Res 2023; 37: 5599-621.
27. Emran TB, Islam F, Nath N, et al. Naringin and naringenin polyphenols in neurological diseases: understandings from a therapeutic viewpoint. Life (Basel) 2022; 13: 99.
Outlines

/