Ning Zhang, Hongxian Zhang, Jianning Guo, Yaluan Ma, Xue Bai, Ning Ma, Xiaoxiao Ji, Yanli Meng, Huifang Li, Tananan Sangwanit, Yixin Shi, Jing Zhao, Xiang Li, Jingyuan Lin, Xia Cui
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After the intervention of 28 days, behavioral tests, Nissl staining, Western blot, immunofluorescence, colorimetry, and ELISA were performed to evaluate the pharmacological effects of JPZDD. Proteomics and network pharmacology predicted targets, validated by Western blot.</p><p><strong>Results: </strong>JPZDD alleviated stereotypic behaviors, hippocampal pathology, and modulated glucose metabolites (GLU, pyruvate, lactate, ATP). It downregulated GLUT1, GLUT3, HK2, and LDHA levels while upregulating PDHA level. Besides, JPZDD balanced M1/M2 microglial phenotypes, reducing IL-1β and IL-6 and increasing IL-4 and IL-10. UPLC-MS/MS identified 44 active ingredients and 123 targets; proteomics revealed 28 differentially expressed proteins. GO/KEGG analysis implicated that the PI3K/AKT/mTOR pathway may be the molecular target. JPZDD inhibited PI3K, AKT, and mTOR phosphorylation.</p><p><strong>Conclusion: </strong>JPZDD (16 g·kg⁻¹·d⁻¹) alleviates motor tics, modulates microglial activation and glucose metabolism, and downregulates the PI3K/AKT/mTOR pathway, providing a mechanistic basis for its therapeutic role in TS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3139-3158"},"PeriodicalIF":4.7000,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034289/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring the Therapeutic Mechanism of Jianpi Zhidong Decoction on Tourette Syndrome Based on Proteomics and Network Pharmacology.\",\"authors\":\"Ning Zhang, Hongxian Zhang, Jianning Guo, Yaluan Ma, Xue Bai, Ning Ma, Xiaoxiao Ji, Yanli Meng, Huifang Li, Tananan Sangwanit, Yixin Shi, Jing Zhao, Xiang Li, Jingyuan Lin, Xia Cui\",\"doi\":\"10.2147/DDDT.S505173\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To explore the pharmacological effects of Jianpi Zhidong Decoction (JPZDD) on Tourette Syndrome (TS) using proteomics and network pharmacology.</p><p><strong>Materials and methods: </strong>Chemical components of JPZDD were identified via UPLC-MS/MS. Chronic restraint stress TS model was established by intraperitoneal injection of iminodipropionitrile (IDPN) for 1 week with restraint stress for 3 weeks. Sixty male SD rats were divided into control, model, Tiapride (Tia), and JPZDD groups. After the intervention of 28 days, behavioral tests, Nissl staining, Western blot, immunofluorescence, colorimetry, and ELISA were performed to evaluate the pharmacological effects of JPZDD. Proteomics and network pharmacology predicted targets, validated by Western blot.</p><p><strong>Results: </strong>JPZDD alleviated stereotypic behaviors, hippocampal pathology, and modulated glucose metabolites (GLU, pyruvate, lactate, ATP). It downregulated GLUT1, GLUT3, HK2, and LDHA levels while upregulating PDHA level. Besides, JPZDD balanced M1/M2 microglial phenotypes, reducing IL-1β and IL-6 and increasing IL-4 and IL-10. UPLC-MS/MS identified 44 active ingredients and 123 targets; proteomics revealed 28 differentially expressed proteins. 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Exploring the Therapeutic Mechanism of Jianpi Zhidong Decoction on Tourette Syndrome Based on Proteomics and Network Pharmacology.
Purpose: To explore the pharmacological effects of Jianpi Zhidong Decoction (JPZDD) on Tourette Syndrome (TS) using proteomics and network pharmacology.
Materials and methods: Chemical components of JPZDD were identified via UPLC-MS/MS. Chronic restraint stress TS model was established by intraperitoneal injection of iminodipropionitrile (IDPN) for 1 week with restraint stress for 3 weeks. Sixty male SD rats were divided into control, model, Tiapride (Tia), and JPZDD groups. After the intervention of 28 days, behavioral tests, Nissl staining, Western blot, immunofluorescence, colorimetry, and ELISA were performed to evaluate the pharmacological effects of JPZDD. Proteomics and network pharmacology predicted targets, validated by Western blot.
Results: JPZDD alleviated stereotypic behaviors, hippocampal pathology, and modulated glucose metabolites (GLU, pyruvate, lactate, ATP). It downregulated GLUT1, GLUT3, HK2, and LDHA levels while upregulating PDHA level. Besides, JPZDD balanced M1/M2 microglial phenotypes, reducing IL-1β and IL-6 and increasing IL-4 and IL-10. UPLC-MS/MS identified 44 active ingredients and 123 targets; proteomics revealed 28 differentially expressed proteins. GO/KEGG analysis implicated that the PI3K/AKT/mTOR pathway may be the molecular target. JPZDD inhibited PI3K, AKT, and mTOR phosphorylation.
Conclusion: JPZDD (16 g·kg⁻¹·d⁻¹) alleviates motor tics, modulates microglial activation and glucose metabolism, and downregulates the PI3K/AKT/mTOR pathway, providing a mechanistic basis for its therapeutic role in TS.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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