Targeted Energy Metabolomics Combined with Spatial Metabolomics Study on the Efficacy of Guhong Injection Against Cerebral Ischemia Reperfusion

Optimizing the metabolic phenotype to improve cerebral function is critical for treatment of cerebral ischemia-reperfusion (I/R) injury. Guhong injection (GHI), which comprised safflower extract and aceglutamide, is widely prescribed in Chinese medicine for the treatment of cerebrovascular diseases. In this study, a combination of LC-QQQ-MS and MALDI-MSI were utilized to explore tissue-specific metabolic alterations in the brain of I/R, as well as to evaluate the therapeutic effect of GHI. Pharmacological evaluation demonstrated that GHI can significantly improve infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. Based on LC-QQQ-MS, 23 energy metabolites were found to be significantly altered in the I/R group compared to the sham group (P < 0.05). After GHI treatment, 12 metabolites, including G6P, TPP, NAD, citrate, succinate, malate, ATP, GTP, GDP, ADP, NADP, and FMN showed a significant tendency of returning to baseline values (P < 0.05). Based on MALDI-MSI, 4 metabolites in glycolysis and TCA, 4 metabolites in nucleic acid metabolism, 4 amino acid metabolites, and 6 metabolites were discovered and compared between the different groups in the four special regions of cortex, hippocampus, hypothalamus, and striatum. Parts of these were found to have significant changes after I/R in the special brain region, and were regulated by GHI. The study provides comprehensive and detailed information for specific metabolic reprogramming of brain tissue in rats with I/R, and the therapeutic effect of GHI.

Automated summary

LC-QQQ-MS and MALDI-MSI were used to study the effect of cerebral ischemia-reperfusion (I/R) injury and the therapeutic effect of Guhong injection (GHI) on tissue-specific metabolic alterations in the brain. GHI significantly improved infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. LC-QQQ-MS identified 23 altered energy metabolites in the I/R group, while 12 metabolites showed a significant tendency of returning to baseline values after GHI treatment. MALDI-MSI revealed differential expression of metabolites in specific brain regions, which were regulated by GHI.