| 摘要 |
This study was conducted to explore the action mechanism of limonoids against Alzheimer’s disease (AD) based on network pharmacology and molecular docking techniques. [Methods] Limonoid compounds were obtained through literature research (January 1942 to January 2021). Active components and potential targets of limonoids were retrieved from PubChem, TCMSP, and Swiss Target Prediction databases. AD-related targets were obtained from the GeneCards database, and intersecting targets were identified using Venny 2.1.0 to obtain the action targets of limonoids against AD. The protein-protein interaction (PPI) network was constructed using the String platform, and key targets were screened and visualized via network topology analysis with Cytoscape software. GO and KEGG pathway enrichment analyses were performed using the Metascape database, and a "drug-component-target-pathway-disease" network diagram was constructed using Cytoscape. AutoDock was empolyed for molecular docking to predict the binding properties of limonoid active components and their targets. [Results] A total of 60 limonoid compounds were obtained from literature research. Network pharmacology analysis showed 58 effective active components and 134 common targets between limonoids and AD. Key targets included AKT1 (serine/threonine-protein kinase 1), TNF (tumor necrosis factor), STAT3 (signal transducer and activator of transcription 3), BCL2 (B-cell lymphoma 2), and EGFR (epidermal growth factor receptor). KEGG enrichment analysis revealed key signaling pathways such as pathways in cancer, Kaposi sarcoma-associated herpesvirus infection, PI3K-Akt signaling pathway, lipid and atherosclerosis, proteoglycans in cancer, MAPK signaling pathway, and Ras signaling pathway. Molecular docking results indicated that aphanamixoid A, obacunol, cipadesin C, harpertrioate A, xylogranatin A, 11-oxocneorin G, evodulone, methyl angolensate, harrpemoid B and khivorin may be key components of limonoids against AD. [Conclusions] Limonoids exert anti-Alzheimer’s effects through a multi-molecule, multi-target and multi-pathway mechanism. |
