Metabolomics and network pharmacology analysis of mechanisms underlying amelioration of tic disorders in rats by Jiawei Huangan Lipi decoction.

OBJECTIVE: To further investigate the mechanism of Jiawei Huangan Lipi decoction (, 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.