Investigating the pharmaceutical substances and action mechanisms of Changmaxifeng granules against tic disorders

Abstract

Background: Tic disorders (TDs) are a type of neurological and psychiatric disorder characterized by vocal or motor tics in the head, body, or limbs. Clinical studies have shown that Changmaxifeng granules (CG) can treat TDs. However, the pharmaceutical substances and mechanism of action of CG remain unclear.

Aim: To investigate the pharmaceutical substances and action mechanisms of CG against TDs, this study employs serum medicinal chemistry, network pharmacology, and molecular docking analysis.

Methods: Ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry was used to identify the blood-absorbed constituents of CG; Network pharmacology was then used to integrate these compounds with disease targets, followed by protein-protein interaction (PPI) networks analysis to pinpoint key proteins. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses combined with molecular docking elucidated the underlying mechanism of action.

Results: Overall, 187 chemical components, including terpenoids, sugars, phenolic acids, and flavonoids, were identified in vitro. In addition, 75 components, namely 49 prototype components and 26 metabolites, were identified in vivo. The PPI results revealed 225 overlapping targets, with TNF, IL-6, FOS, VEGFA, and ESR1 being the major targets. GO and KEGG analyses were performed to identify key signaling pathways and biological processes. Paeonol, evofolin B, aspalathin, and paeoniflorin were identified as potential pharmacodynamic substances based on the results of the "compound-target" network. The maximum binding energy between the core target and the active ingredient was less than -4.7 kcal/mol, indicating that the pharmacophore exhibited a strong affinity toward the core ingredient.

Conclusion: This study elucidated the in vitro and in vivo chemical components of CG and outlined their potential targets and action mechanisms. This study provides a basis for further research into the action mechanism and clinical application of CG.

Keywords: Against tic disorders; Changmaxifeng granule; Chemical components; Molecular docking; Network pharmacology.