Cerebral ischemia-reperfusion (CIR) injury occurs as a secondary injury during the treatment of ischemic stroke (IS). There is a high death rate and morbidity due to IS throughout the world. Even though Naoxintong Capsule (NXT) is effective in the treatment of CIR, its mechanisms of action are unclear. The study aims to explore the clear mechanism associated with NXT therapy for CIR. We established the model of middle cerebral artery occlusion to evaluate the neurological function and assess the infarct size. Brain tissue metabolomics was used to identify different metabolites, and metabolic profiling systems enriched metabolic pathways. Then, the potential targets of NXT in the treatment of CIR were explored by proteomic, transcriptomic, and metabolomic methods. NXT improves CIR symptoms. We found potential 11 proteins and corresponding metabolites involved in NXT treatment of CIR. Most of these metabolites are regulated to restore after treatment. According to network pharmacology, we found 6 hub genes, including Glb1, Gmps, Pfas, Atic, Gaa, and Acox1, and their associated core metabolites and pathways. This study reveals the complex mechanism of NXT in treating CIR, and provides a new strategy for future researchers to screen related targets and pathways.
Keywords: Naoxintong Capsule; cerebral ischemia-reperfusion injury; metabolomics; multiomics; proteomics; transcriptomics.