OBJECTIVE To explore the mechanism of Ginseng Radix et Rhizoma-Ziziphi Spinosae Semen in treatment of Parkinson’s disease based on UHPLC-TOF-MS, network pharmacology and molecular docking technologies.

METHODS UHPLC-TOF-MS was used to qualitatively identify the constituents of Ginseng Radix et Rhizoma-Ziziphi Spinosae Semen migrated into blood. Targets of the plasma constituents and the disease associated target were retrieved from Swiss Target Prediction and Gene Cards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.10.0 was employed to construct the “compound-target-pathway” network and the targets of Ginseng Radix et Rhizoma-Ziziphi Spinosae Semen against Parkinson’s disease were predicted. The Auto Dock software was used for molecular docking analysis of key targets and active ingredients. Additionally, an SH-SY5Y cell model was used to further verify the protective effects of ginsenoside Rg1 and lotusine against MPP-induced damage. Cell viability was assessed using the CCK-8 assay, and apoptosis was evaluated by TUNEL fluorescence staining.

RESULTS A total of 20 constituents of Ginseng Radix et Rhizoma-Ziziphi Spinosae Semen migrated into blood were identified, mainly including triterpenoid saponins and alkaloids. The 78 key targets were screened out by PPI. KEGG enrichment showed that Ginseng Radix et Rhizoma-Ziziphi Spinosae Semen might play a role in treatment of Parkinson’s disease through PI3K-Akt, Rap1, Prolactin and other pathways. Molecular docking results showed that key targets MAPK1, AKT1, MAPK8, HRAS, EGFR could be well combined by core active constituents ginsenoyne B, ginsenoside Rg1, zizyphusine, ginsenoside Rf, lotusine, respectively. Cell experiments showed that compared with the model group, ginsenoside Rg1 and lotusine significantly increased cell viability, reduced the proportion of TUNEL-positive cells, and exhibited more pronounced protective effects when used in combination.

CONCLUSION Ginseng Radix et Rhizoma-Ziziphi Spinosae Semen can play a role in the prevention and treatment of Parkinson’s disease through multiple components, targets and pathways. Furthermore, its representative core components demonstrate neuroprotective effects in a human neuronal cell model.