Abstract
BACKGROUND: Da Chuan Xiong Fang (DCXF) is a traditional Chinese medicine (TCM) formula used to treat migraines. Previously, we uncovered partial mechanisms involved in the therapeutic actions of DCXF on migraines. METHODS: In this study, we further elucidated its antimigraine mechanisms in vivo by using an integrated strategy coupling with network pharmacology and metabolomics techniques. RESULTS: Network pharmacology identified 33 genes linked with both migraine and DCXF, most of which were 5-hydroxytryptamine receptors, dopamine, and peptide receptors. The results of GO and KEGG enrichment analysis showed that DCXF significantly regulated tyrosine metabolism, tryptophan metabolism, dopamine metabolic process, glucose transmembrane transport, lipid metabolism, and fatty acid transport. The results of metabolomics analysis found that the metabolism of tryptophan and tyrosine in the brain tissue and energy and lipid metabolism of rats tended towards normal and reached normal levels after administering DCXF. The metabolomics and network pharmacology approaches demonstrated similar antimigraine effects of DCXF on endogenous neurotransmitters and overall trends in serum and brain tissue. Using both approaches, 62 hub genes were identified from the protein-protein interaction (PPI) network of DCXF and gene-metabolite interaction network, with hub genes and different metabolites in serum and brain tissue. The hub genes of DCXF, which were mostly linked with inflammation, might affect mainly neurotransmitters in serum and brain tissue metabolisms. CONCLUSION: Network pharmacology and metabolomics study may help identify hub genes, metabolites, and possible pathways of disease and treatment. Additionally, two parts of the results were integrated to confirm each other. Their combination may help elucidate the relationship between hub genes and metabolites and provide the further understanding of TCM mechanisms.