Objective To explore the mechanisms of Tongmai granules in treatment of stroke based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and network pharmacology technology.

Methods The chemical compounds of Tongmai granules were identified by UHPLC-QTOF-MS approach. The compounds' targets and stroke-related targets were screened via TCMSP, TTD and PubMed databases. STRING database was used to construct the protein interaction network of key targets. DAVID database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for key targets.

Results A total of 96 chemical components, such as salvianolic acid B, puerarin and ligustilide were identifiedfrom Tongmai granules. A total of 38 active compounds and 55 targets of Tongmai granules for stroke treatment were obtained. The core targets included prostaglandin-endoperoxide synthase 2 (PTGS2), nuclear factor kappa B (NFκB)as well as nuclear factor erythroid 2-related factor 2 (NRF2) and so on, and the key pathways mainly involved hypoxia-inducible factor-1 (HIF-1), tumor necrosis factor (TNF) and phosphatidylinositol 3-kinase (PI3K)-Akt and so on.

Conclusion Major active components such as salvianolic acid B, puerarin and ligustilide in Tongmai granules regulate HIF-1, TNF and PI3K-Akt signaling pathways by acting on PTGS2, NFκB and NRF2 and other targets to play an anti-stroke role.