부산대학교 도서관

Mild cognitive impairment (MCI) is a transitional condition between normality and de mentia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fullyunderstood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinityresponsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry(LCeMS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI)network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, weassessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial functionby measuring the activity of the mitochondrial respiratory chain complex and performing moleculardocking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related proteintargets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mito chondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial func tion analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd andmitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chaincomplex I and regulating mitochondrial function, supporting ginseng's therapeutic application incognitive deficits.