Combined cell membrane solid-phase chromatography and microdialysis-based metabolomics to explore the material basis of Chaihu Shugan San against post-stroke depression

Chaihu Shugan San (CSS) has a good therapeutic effect on post-stroke depression (PSD), but its pharmacodynamic material basis is still unclear. This study revealed the pharmacodynamic material basis of CSS against PSD based on cell membrane solid-phase chromatography and hippocampal metabolomics. Therefore, the specific binding components of CSS and HT22 cells were screened by cell membrane solid-phase chromatography combined with ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) technique, and their effects on the viability and brain-derived neurotrophic factor (BDNF) of injured HT22 cells were evaluated. Conduct metabolomics on the hippocampus of PSD rats with the intervention of CSS combining the brain microdialysis technique and UPLC-Q-TOF-MS, and biological networks were constructed to reveal the mechanism of action of CSS anti-PSD, and molecular docking was performed to evaluate the binding ability of HT22 specific binding components to target proteins. The results showed that 8 specific binding components of CSS and HT22 cells were identified by cell membrane solid-phase chromatography. Except for Nobiletin, the other 7 components could protect HT22 cells and significantly increase BDNF levels. The UPLC-Q-TOF-MS technique identified 13 differential metabolites in metabolomics. Biological network analysis revealed that glutathione metabolism might be an important pathway for CSS anti-PSD. The specific binding component of HT22 was well-bound to the target protein.