Mechanism of Sanhua Decoction Against Cerebral Ischemia–Reperfusion Injury by Serum Pharmacochemistry, Network Pharmacology, and Metabolomics

Cerebral ischemia-reperfusion injury (CIRI) is classified under the category of stroke. Sanhua Decoction (SHD) is a classic prescription for the treatment of stroke, but its pharmacodynamic material basis and mechanism of action have not been fully elucidated. This study aimed to elucidate the bioactive components and therapeutic mechanisms of SHD against CIRI by integrating serum pharmacochemistry, network pharmacology, and metabolomics. Using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry, a 22 absorbed SHD prototype compounds were identified from rat serum. Through the application of network pharmacology and molecular docking technology, it was concluded that the key active ingredients, such as marmesin and aloe-emodin, mainly play a therapeutic role through key targets such as steroid receptor coactivator (SRC) and protein kinase B1 (AKT1). Molecular docking showed that these targets had strong affinity with key compounds. The results of pharmacodynamics showed that SHD could improve the neurological function score of CIRI rats, reduce the infarct area, and improve the pathological changes of brain tissue. Metabolomics analysis showed that SHD may play a therapeutic role by regulating steroid hormone synthesis and ubiquinone-related pathways. This study provides a methodological framework for exploring the role of Chinese herbal compounds in the treatment of CIRI.