Integration of Multiple Mass Spectrometry Techniques and Molecular Network Analysis With Bioinformatics Approaches Revealed the Mechanism of Jiuwei Xifeng Granules in the Treatment of Tourette's Syndrome

RATIONALE: Jiuwei Xifeng Granules, a Chinese patent medicine developed based on renowned traditional Chinese medicine, has shown significant clinical efficacy in treating Tourette's syndrome. However, there is limited research on its pharmacological compounds and mechanism of action. METHODS: In this study, high-resolution mass spectrometry (HRMS) was employed to analyze the natural organic small molecules in the herbal ingredients of Jiuwei Xifeng Granules and the drug-derived components in the serum, liver, and brain tissues of mice following long-term administration, as well as the protein components in the animal drugs. Meanwhile, inorganic trace elements are also widely assessed in Jiuwei Xifeng Granules. Molecular network analysis is utilized to further analyze the natural organic small molecules. Finally, network pharmacology and molecular docking techniques were employed to investigate the mechanisms of action of the main active ingredients. RESULTS: In total, 51 natural organic small molecules were identified in the five herbal medicines of Jiuwei Xifeng Granules, and the main active components included Gastrodin, Gentiopicroside, and Geissoschizine methyl ether. A total of 22 drug-derived components were identified in the blood of mice, 18 components were detected in the liver, and 8 were found in the brain tissue. Molecular network analysis further expanded the range of identified natural small molecule organic compounds. Thirty-six proteins were identified from two animal drugs in Jiuwei Xifeng Granules, and 68 trace elements were identified from two mineral medicines in Jiuwei Xifeng Granules. The results of the systems pharmacology analysis confirm that the pharmacological action pathways include serotonergic synapse, neuroactive ligand-receptor interaction, dopaminergic synapse, and cAMP signaling pathway. The main targets included DRD2, SLC6A4, HTR1A, DRD1, and KCNH2. CONCLUSION: This study employed a multi-omics approach to comprehensively analyze the active compounds in Jiuwei Xifeng Granules, providing a chemical foundation for elucidating its mechanism of action in treating Tourette's syndrome.