Untargeted cell metabolomics and network analysis of CORT-Injured HT22 cells treated with albiflorin

Albiflorin (AF) is a natural monoterpene glycoside compound found in the traditional Chinese medicine Paeonia lactiflora , which has been found to have good antidepressant effects. To investigate its protective effect against corticosterone (CORT) -induced HT22 cell injury, CORT-injured HT22 cell model was established. The apoptosis rate of the cells was measured by flow cytometry, and the levels of NO, GABA, Glu, and HIAA in the cell supernatant were analyzed. An untargeted metabolomic study was conducted using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), combined with network analysis to identify the targets of AF's action in CORT-injured HT22 cells. The results showed that the apoptosis rate, Glu, and NO levels were significantly increased, while GABA and 5-HIAA levels were significantly decreased after CORT injury, and AF could significantly reverse the trend. Cell metabolomics results revealed that AF notably improved the metabolomic profile of CORT-injured HT22 cells. Major metabolic pathways involved glutathione metabolism, taurine and hypotaurine metabolism, nicotinic acid and nicotinamide metabolism. Network analysis indicated that GSR, GGT1, GPX6, GPX5, GPX2 may be key targets involved in the protection of CORT-injured HT22 cells. Molecular docking and molecular dynamics simulations showed that AF binds well to them. In conclusion, AF can protect CORT-injured HT22 cells, and its mechanism of action may be related to the regulation of glutathione metabolism, taurine and hypotaurine metabolism, nicotinic acid and nicotinamide metabolism.