Analysis of cerebrospinal fluid metabolites affected by WenDanTang based on ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry

WenDanTang (WDT) is a Chinese herbal formula used to treat various diseases, including neurodegenerative diseases. However, the neuroprotective metabolic pathways and the components involved in this process are not fully understood. In this study, we examined the neuroprotective metabolic pathways of WDT in rat brains using cerebrospinal fluid metabolomics and ultra‐high‐performance liquid chromatography–high‐resolution mass spectrometry. Twelve rats were randomly divided into a WDT (administrated with WDT solution) and a control group. The ultra‐high‐performance liquid chromatography technique was used to explore the components of the WDT solution and cerebrospinal fluid, and secondary mass spectra of cerebrospinal fluid were used to identify possible brain‐incorporating components after WDT. The results of the differential metabolism analysis showed that eight metabolites were typically altered (all p < 0.05). By comparing the secondary mass spectra of the cerebrospinal fluid of rats and WDT solution, two possible brain‐incorporating components of WDT, stachydrine and α‐methoxyphenylacetic acid, were identified. The data also suggested that WDT affects nucleotide metabolism, glutathione metabolism, and B‐vitamin metabolic pathways, the central differential metabolic pathways. These data suggest that WDT protects neurons through its active components, such as stachydrine, and regulates biochemical metabolism to affect the brain's energy metabolism and antioxidant capacity.