Four-Dimensional Label-Free Quantitative Proteomics of Ginsenoside Rg2 Ameliorated Scopolamine-Induced Memory Impairment in Mice through the Lysosomal Pathway

Alzheimer's disease (AD) is a neurodegenerative disease. Ginsenoside Rg₂ has shown potential in treating AD, but the underlying protein regulatory mechanisms associated with ginsenoside Rg₂ treatment for AD remain unclear. This study utilized scopolamine to induce memory impairment in mice, and proteomics methods were employed to investigate the potential molecular mechanism of ginsenoside Rg₂ in treating AD model mice. The Morris water maze, hematoxylin and eosin staining, and Nissl staining results indicated that ginsenoside Rg₂ enhanced cognitive ability and decreased neuronal damage in AD mice. Proteomics, western blot, and immunofluorescence results showed that ginsenoside Rg₂ primarily improved AD mice by downregulating the expression of LGMN, LAMP1, and PSAP proteins through the regulation of the lysosomal pathway. Transmission electron microscopy and network pharmacology prediction results showed a potential connection between the mechanism of ginsenoside Rg₂ treatment for AD mice and lysosomes. The comprehensive results indicated that ginsenoside Rg₂ may improve AD by downregulating LGMN, LAMP1, and PSAP through the regulation of the lysosomal pathway.