Integrated metabolomics and network pharmacology leveraging UPLC-Q-TOF-MS reveal material basis and metabolic mechanisms underlying Tongqiao Huoxue Decoction's efficacy in cerebral infarction.

Abstract

Cerebral infarction (CI) is a common manifestation of stroke, which is a form of cerebral ischaemia. Tongqiao Huoxue Decoction (THD) is a proven therapeutic formulation for stroke treatment. As a therapeutic formulation renowned for promoting blood circulation and removing blood stasis, it is widely applied in clinical practice. However, the molecular mechanisms underlying its therapeutic effects are not yet clear. The purpose of this study is to evaluate the therapeutic effects of THD in CI rats and to delve into its potential mechanisms of action through pharmacodynamic experiments and metabolomic analysis. Results demonstrated that THD treatment was associated with reduced symptoms and metabolic disturbances in CI rats. Metabolomics analysis revealed the therapeutic effects of THD, modulating levels of 31 differential metabolites in urine and 41 in blood. These effects were associated with biosynthesis of unsaturated fatty acid, Glycerophospholipid metabolism, Arachidonic acid metabolism, Sphingolipid metabolism, Taurine and Hypotaurine metabolism, Glutathione metabolism, Linoleic acid metabolism. Network pharmacology revealed 49 bioactive compounds targeting 407 targets involved in Lipid and atherosclerosis, PI3K-Akt signaling, and Calcium signaling pathways. Finally, molecular docking analysis was performed to evaluate the binding interactions between the compounds from THD and the potential targets. Based on the results, kaempferol was thus suggested as a candidate bioactive constituent. These findings contribute to a better understanding of CI pathogenesis and provide a basis for further investigations into THD.