Background: Stroke is ranked second among diseases that cause mortality worldwide. Owing to its complicated pathogenesis, no satisfactory treatment strategies for stroke are available. Dachengqi decoction (DCQD), a traditional Chinese herbal medicine, has been widely used in China for a long time, as it has a good effect on stroke. However, the molecular mechanism underlying this effect of DCQD is unclear.

Objective: In the present study, we aimed to reveal and explore the multi-pathway and multi-gene regulatory molecular mechanism of Dachengqi decoction in the treatment of stroke.

Methods: In this study, a network pharmacology method, in combination with oral bioavailability prediction and drug-likeness evaluation, was employed to predict the active ingredients of DCQD. The target genes of the active components and the traced pathways related to these target genes were predicted. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using clusterProfiler software package on the R platform and ClueGo+CluePedia plug-ins. Finally, the key DCQD targets were verified using the Gene Expression Omnibus (GEO) dataset.

Results and Discussion: According to the ADME model, 52 active components were screened from 296 active components of DCQD. After prediction and screening, 215 stroke-related targets were obtained and analyzed via GO and KEGG analyses. GO analysis showed that DCQD targets were mainly involved in the regulation of oxidative stress, lipid metabolism, inflammation, and other biological processes. KEGG pathway analysis further revealed pathways involved in stroke, such as arachidonic acid metabolic, HIF-1 signaling pathway, estrogen signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, platelet activation pathway, VEGF signaling pathway, and cAMP signaling pathway. Network analysis revealed that DCQD might be involved in the regulation of lipid metabolism, blood pressure, inflammation, angiogenesis, neuroprotection, platelet aggregation, apoptosis, and oxidation in stroke treatment. GEO dataset analysis showed that DCQD’s therapeutic effects might be exerted via the bidirectional regulation principle.

Conclusion: Based on the methods of network pharmacology and GEO analysis, it was found that, during stroke treatment, DCQD regulates and controls multiple genes and multiple pathways in a synergistic manner, providing a new strategy for stroke treatment.