Molecular Mechanism of Ginseng-Schisandrae Herb Pair in Improving Neurodegenerative Disease on a Network Pharmacology and Molecular Docking

Abstract

Background: This study aims to explore the active components of Panax Ginseng (PG)-Schisandrae Chinensis Fructus (SC) and reveal the mechanism of improving neurodegenerative diseases (NDD) based on network pharmacology and molecular docking. Methods: Detailed information about the PG-SC herbal pair was obtained from traditional Chinese medicine systems pharmacology (TCMSP) and screened using OB (oral bioavailability) ≥30% and DL (drug-likeness) ≥0.18 as criteria. Genes were collected using OMIM, Genecards, and PharmGKB (Pharmacogenetics and Pharmacogenomics Knowledge Base) methods. The string database was utilized to obtain protein-protein interaction (PPI) data. The core targets were entered into the “Data Source” of the eFP (electronic Fluorescent Pictograph) browser (http://bar.utoronto.ca/efp_human/) for organ localization and created a target-organ localization map. We constructed and analyzed the network using Cytoscape 3.9.1 (National Institute of General Medical Sciences, Bethesda, MD, USA). Encyclopedia of genomes (KEGG) pathway-enriched targets were used for analysis. After identifying the core network, a protein-protein interaction (PPI) network of PG-SC targets was constructed. Autodock Vina and PyMOL software were used to validate the results for its active ingredients and key targets. Results: There were 14 active ingredients in Ginseng and 8 in Schisandra, with 8320 corresponding protein targets and 80 common targets with neurodegenerative diseases (NDD), of which 21 highly abundant targets were highly expressed in the brain. Six core targets were identified, including AKT1 (RAC-alpha serine/threonine-protein kinase), CASP3 (Caspase 3), MAPK8 (Mitogen-Activated Protein Kinase 8), 1L1B (Interleukin 1 Beta), JUN (Jun Proto-Oncogene, AP-1 Transcription Factor Subunit), and PTGS2 (Prostaglandin-Endoperoxide Synthase 2). The 142 KEGG signaling pathways were enriched, including the pathways of neurodegeneration-multiple diseases and neuroactive ligand-receptor interaction. Molecular docking confirmed that the core targets (AKT1, CASP3, MAPK8, 1L1B, JUN, PTGS2) could bind to the active compounds (Kaempferol, Beta_sitosterol, Ginsenoside Rh₂, Stigmasterol, Inermin, Dianthramine, Arachidonate, Frutinone A, Girinimbin, Suchilactone, Fumarine). Conclusions: Based on network pharmacology and molecular docking, the PG-SC herbal pair could act on NDD through neuronal programmed cell death targets and related signaling pathways. Our findings provide the basis for further research using herbs to treat NDD and develop anti-NDD drugs.