Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (4): 916-926.DOI: 10.19852/j.cnki.jtcm.2026.04.012
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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 Lijin1, CHEN Linghui2, WANG Chengrui3, FANG Yijun2, GAN Liping4, HANG Jinyu2(
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Department of Pharmacy ,Zhangzhou Traditional Chinese Medical Hospital Zhangzhou 363000, China
2Department of Pediatrics ,Zhangzhou Traditional Chinese Medical Hospital Zhangzhou 363000, China
3School of Medicine and Health ,Harbin Institute of Technology, Harbin150001, China; Zhengzhou Advanced Research Institute of Harbin Institute of Technology Zhengzhou 450000, China
4Department of aircrew ,General Hospital of Xinjiang Military Region Urumqi 830000, China
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Received:2025-05-28Accepted:2025-11-07Online:2026-08-15Published:2026-08-08 -
Contact:HANG Jinyu, Department of Pediatrics, Zhangzhou Traditional Chinese Medical Hospital, Zhangzhou 363000, China. sx11b@163.com,Telephone: +86-13709333668
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Supported by:Fujian Natural Science Foundation: Mechanisms of Jiawei Huangan Lipi decoction in Treating Tic Disorders Investigated by Network Pharmacology and Metabolomics(2023J011851)
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.
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Table 1 Comparison of scores between different groups ($\bar{x}±s$)
| Item | Group | H value | P value | |||
|---|---|---|---|---|---|---|
| TDM (n = 6) | Low-JHD (n = 6) | Middle-JHD (n = 6) | High-JHD (n = 6) | |||
| Locomotor Behavior | 2.3±0.4 | 1.3±0.7 | 1.5±0.3 | 0.8±0.4 | 15.7 | 0.001 |
| Stereotyped Behavior | 2.2±0.5 | 1.6±0.8 | 1.2±0.5 | 1.1±0.6 | 9.8 | 0.020 |
Table 1 Comparison of scores between different groups ($\bar{x}±s$)
| Item | Group | H value | P value | |||
|---|---|---|---|---|---|---|
| TDM (n = 6) | Low-JHD (n = 6) | Middle-JHD (n = 6) | High-JHD (n = 6) | |||
| Locomotor Behavior | 2.3±0.4 | 1.3±0.7 | 1.5±0.3 | 0.8±0.4 | 15.7 | 0.001 |
| Stereotyped Behavior | 2.2±0.5 | 1.6±0.8 | 1.2±0.5 | 1.1±0.6 | 9.8 | 0.020 |
Figure 1 Network pharmacology of JHD A: venn diagram of the TD targets for JHD; B: PPI network diagram; C: KEGG pathway enrichment bubble map. TD: tic disorders; JHD: Jiawei Huangan Lipi decoction; PPI: protein-protein interaction; KEGG: kyoto encyclopedia of genes and genomes; GO: gene ontology; ICAM1: intercellular adhesion molecule 1; CCL2: chemokine (C-C motif) ligand 2; IL2: interleukin 2; IRFNG: interferon gamma; CD40LG: CD40 ligand; CXCL8: C-X-C motif chemokine ligand 8; IL10: interleukin 10; IL4: interleukin 4; IL1B: interleukin 1 beta; MMP9: matrix metallopeptidase 9; COL18A1: collagen type XVIII alpha 1 chain; SPP1: secreted phosphoprotein 1; CYP1A2: cytochrome P450 family 1 subfamily A member 2; GSTM1: glutathione S-transferase mu 1; CYP3A4: cytochrome P450 family 3 subfamily A member 4; OPRM1: opioid receptor mu 1; OPRD1: opioid receptor delta 1; ACHE: acetylcholinesterase; APP: amyloid beta precursor protein; MTTP: microsomal triglyceride transfer protein; APOB: apolipoprotein B; RUNX2: runt-related transcription factor 2; SLC6A3: solute carrier family 6 member 3; DRD1: dopamine receptor D1; DRD2: dopamine receptor D2; SLC6A4: solute carrier family 6 member 4; STAT3: signal transducer and activator of transcription 3; MAPK1: mitogen-activated protein kinase 1; MARK1: MAP/microtubule affinity regulating kinase 1; FOS: fos proto-oncogene, AP-1 transcription factor subunit; ESR1: estrogen receptor 1; ESR2: estrogen receptor 2; SCN5A: sodium voltage-gated channel alpha subunit 5; KCNH2: potassium voltage-gated channel subfamily H member 2; PPARG: peroxisome proliferator-activated receptor gamma; ADIPOQ: adiponectin; PPARA: peroxisome proliferator-activated receptor alpha; F10: coagulation factor X; F3: coagulation factor Ⅲ, tissue factor; PLAT: plasminogen activator, tissue type; CHEK2: checkpoint kinase 2; GSK3B: glycogen synthase kinase 3 beta; EGFR: epidermal growth factor receptor; EGF: epidermal growth factor; NOS2: nitric oxide synthase 2; ERBB3: erb-B2 receptor tyrosine kinase 3; ERBB2: erb-B2 receptor tyrosine kinase 2; MYC: MYC proto-oncogene, bHLH transcription factor; TP53: tumor protein P53; PTEN: phosphatase and tensin homolog; HSPB1: heat shock protein family B (small) member 1; TGFB1: transforming growth factor beta 1; CRP: C-reactive protein.
Figure 1 Network pharmacology of JHD A: venn diagram of the TD targets for JHD; B: PPI network diagram; C: KEGG pathway enrichment bubble map. TD: tic disorders; JHD: Jiawei Huangan Lipi decoction; PPI: protein-protein interaction; KEGG: kyoto encyclopedia of genes and genomes; GO: gene ontology; ICAM1: intercellular adhesion molecule 1; CCL2: chemokine (C-C motif) ligand 2; IL2: interleukin 2; IRFNG: interferon gamma; CD40LG: CD40 ligand; CXCL8: C-X-C motif chemokine ligand 8; IL10: interleukin 10; IL4: interleukin 4; IL1B: interleukin 1 beta; MMP9: matrix metallopeptidase 9; COL18A1: collagen type XVIII alpha 1 chain; SPP1: secreted phosphoprotein 1; CYP1A2: cytochrome P450 family 1 subfamily A member 2; GSTM1: glutathione S-transferase mu 1; CYP3A4: cytochrome P450 family 3 subfamily A member 4; OPRM1: opioid receptor mu 1; OPRD1: opioid receptor delta 1; ACHE: acetylcholinesterase; APP: amyloid beta precursor protein; MTTP: microsomal triglyceride transfer protein; APOB: apolipoprotein B; RUNX2: runt-related transcription factor 2; SLC6A3: solute carrier family 6 member 3; DRD1: dopamine receptor D1; DRD2: dopamine receptor D2; SLC6A4: solute carrier family 6 member 4; STAT3: signal transducer and activator of transcription 3; MAPK1: mitogen-activated protein kinase 1; MARK1: MAP/microtubule affinity regulating kinase 1; FOS: fos proto-oncogene, AP-1 transcription factor subunit; ESR1: estrogen receptor 1; ESR2: estrogen receptor 2; SCN5A: sodium voltage-gated channel alpha subunit 5; KCNH2: potassium voltage-gated channel subfamily H member 2; PPARG: peroxisome proliferator-activated receptor gamma; ADIPOQ: adiponectin; PPARA: peroxisome proliferator-activated receptor alpha; F10: coagulation factor X; F3: coagulation factor Ⅲ, tissue factor; PLAT: plasminogen activator, tissue type; CHEK2: checkpoint kinase 2; GSK3B: glycogen synthase kinase 3 beta; EGFR: epidermal growth factor receptor; EGF: epidermal growth factor; NOS2: nitric oxide synthase 2; ERBB3: erb-B2 receptor tyrosine kinase 3; ERBB2: erb-B2 receptor tyrosine kinase 2; MYC: MYC proto-oncogene, bHLH transcription factor; TP53: tumor protein P53; PTEN: phosphatase and tensin homolog; HSPB1: heat shock protein family B (small) member 1; TGFB1: transforming growth factor beta 1; CRP: C-reactive protein.
Figure 2 Molecular docking of JHD A: thermogram of the docking binding energies of key JHD components to the core targets; B-E: molecular docking diagram of active ingredients with key targets; B: luteolin docked with ESR1; C: quercetin docked with ESR1; D: naringenin docked with ESR1; E: kaempferol docked with AKT1. JHD: Jiawei Huangan Lipi decoction; ESR1: estrogen receptor 1; AKT1: RAC-alpha serine/threonine kinase 1; IL-6: interleukin 6; TNF: tumor necrosis factor; ARG: arginine; LEU: leucine; HIS: histidine; GLU: glutamic acid; LYS: lysine; ASN: asparagine; SER: serine; THR: threonine; ILE: isoleucine.
Figure 2 Molecular docking of JHD A: thermogram of the docking binding energies of key JHD components to the core targets; B-E: molecular docking diagram of active ingredients with key targets; B: luteolin docked with ESR1; C: quercetin docked with ESR1; D: naringenin docked with ESR1; E: kaempferol docked with AKT1. JHD: Jiawei Huangan Lipi decoction; ESR1: estrogen receptor 1; AKT1: RAC-alpha serine/threonine kinase 1; IL-6: interleukin 6; TNF: tumor necrosis factor; ARG: arginine; LEU: leucine; HIS: histidine; GLU: glutamic acid; LYS: lysine; ASN: asparagine; SER: serine; THR: threonine; ILE: isoleucine.
Figure 3 Validation of core targets Hippocampal tissues were isolated from six groups of mice, and RNA and protein were extracted for RT-qPCR and Western blot analyses, respectively. A: mRNA levels of Akt1 in the six groups were detected by RT-qPCR; B: mRNA levels of IL-6 in the six groups were detected by RT-qPCR; C: mRNA levels of Tnfa in the six groups were detected by RT-qPCR; D: representative Western blot images showing AKT1, IL-6, and TNF-α protein expression across the six groups; E: statistical graphs quantifying the protein levels of AKT1; F: statistical graphs quantifying the protein levels of IL-6; G: statistical graphs quantifying the protein levels of TNF-α. NC: The normal rats. TDM: tic disorder model. Low-JHD: The TDM rats were treated with JHD at a dose of 2.4 g/mL. Medium-JHD: The TDM rats were treated with JHD at a dose of 3.2 g/mL. High-JHD: The TDM rats were treated with JHD at a dose of 4.8 g/mL. Tiapride: The TDM rats were treated with tiapride. RT-qPCR: reverse transcription quantitative polymerase chain reaction; AKT1: AKT serine/threonine kinase 1; IL-6: interleukin 6; TNF-α: tumor necrosis factor α. Statistical analyses were subjected to one-way analysis of variance. Data are shown as the mean ± standard deviation (n = 3). aP < 0.01 versus NC group; bP < 0.05 versus TDM group.
Figure 3 Validation of core targets Hippocampal tissues were isolated from six groups of mice, and RNA and protein were extracted for RT-qPCR and Western blot analyses, respectively. A: mRNA levels of Akt1 in the six groups were detected by RT-qPCR; B: mRNA levels of IL-6 in the six groups were detected by RT-qPCR; C: mRNA levels of Tnfa in the six groups were detected by RT-qPCR; D: representative Western blot images showing AKT1, IL-6, and TNF-α protein expression across the six groups; E: statistical graphs quantifying the protein levels of AKT1; F: statistical graphs quantifying the protein levels of IL-6; G: statistical graphs quantifying the protein levels of TNF-α. NC: The normal rats. TDM: tic disorder model. Low-JHD: The TDM rats were treated with JHD at a dose of 2.4 g/mL. Medium-JHD: The TDM rats were treated with JHD at a dose of 3.2 g/mL. High-JHD: The TDM rats were treated with JHD at a dose of 4.8 g/mL. Tiapride: The TDM rats were treated with tiapride. RT-qPCR: reverse transcription quantitative polymerase chain reaction; AKT1: AKT serine/threonine kinase 1; IL-6: interleukin 6; TNF-α: tumor necrosis factor α. Statistical analyses were subjected to one-way analysis of variance. Data are shown as the mean ± standard deviation (n = 3). aP < 0.01 versus NC group; bP < 0.05 versus TDM group.
Figure 4 Cross-tabulation analysis of metabolic components A: venn diagram of metabolites in the serum metabolic profile; B: metabolic pathways of the TD metabolites. TD: tic disorders; JHD: Jiawei Huangan Lipi decoction; TDM: tic disorders model.
Figure 4 Cross-tabulation analysis of metabolic components A: venn diagram of metabolites in the serum metabolic profile; B: metabolic pathways of the TD metabolites. TD: tic disorders; JHD: Jiawei Huangan Lipi decoction; TDM: tic disorders model.
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