Hepatic Metabolomics Combined with Network Pharmacology Approach to Reveal The Correlation of Anti-Depression Effect and Nourishing Blood Effect of Angelicae Sinensis Radix

Angelicae Sinensis Radix (AS) has been proved to exert anti-depression effect (ADE) and nourishing blood effect (NBE) in rat model of depression. The correlation of two therapeutic effects and its underlying mechanisms deserved further study. The purpose of this study was to explore the underlying mechanisms of the correlation between ADE and NBE of AS based on hepatic metabonomics, network pharmacology and molecular docking. Metabolomics analysis found that 30 metabolites participate in 11 metabolic pathways were identified as potential metabolites for depression. Further principal component analysis and correlation analysis showed that glutathione, sphinganine, and ornithine were related to pharmacodynamics indicators including behavioral indicators and haematological indicators, indicating that metabolic pathways such as sphingolipid metabolism were in ADE and NBE of AS. Target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis, and a total of 107 pathways were collected. 37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer (UPLC-Triple-TOF/MS) in AS extract passed the filtering criteria were used for network pharmacology, and 46 targets were associated with ADE and NBE of AS. Pathway enrichment analysis further indicated that sphingolipid metabolism were in ADE and NBE of AS. Molecular docking analysis showed that the E-Ligustilide in AS extract had strong binding activity with target protein (PIK3CA, PIK3CD) in sphingolipid metabolism. Our results demonstrated that sphingolipid metabolic pathway was the core pathway in the mechanism of the correlation between ADE and NBE of AS.