Research Paper Volume 13, Issue 14 pp 18993—19012
A network pharmacology approach to uncover the key ingredients in Ginkgo Folium and their anti-Alzheimer’s disease mechanisms
- 1 Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Huazhong University of Science and Technology, Wuhan 430030, China
- 2 School of Medicine, Jianghan University, Wuhan 430056, China
Received: June 1, 2021 Accepted: July 10, 2021 Published: July 27, 2021
https://doi.org/10.18632/aging.203348How to Cite
Copyright: © 2021 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
This study aimed to identify potential anti-Alzheimer’s disease (AD) targets and action mechanisms of Ginkgo Folium (GF) through a network pharmacology approach. Eighty-four potential targets of 10 active anti-AD ingredients of GF were identified, among which genkwanin (GK) had the greatest number of AD-related targets. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathway of GF against AD was Alzheimer disease (hsa05010). More importantly, 29 of the 84 targets were significantly correlated with tau, Aβ or both Aβ and tau pathology. In addition, GO analysis suggested that the main biological processes of GF in AD treatment were the regulation of chemical synaptic transmission (GO:0007268), neuron death (GO:0070997), amyloid-beta metabolic process (GO:0050435), etc. We further investigated the anti-AD effects of GK using N2A-APP cells (a classical cellular model of AD). Treatment N2A-APP cells with 100 μM GK for 48 h affected core targets related to tau pathology (such as CDK5 and GSK3β). In conclusion, these findings indicate that GF exerts its therapeutic effects on AD by acting directly on multiple pathological processes of AD.
Abbreviations
AD: Alzheimer’s disease; GF: Ginkgo Folium; GK: genkwanin; Aβ: amyloidβ; NMDA: N-methyl-D-aspartic acid; TCMSP: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform; OB: oral bioavailability; DL: drug likeness; BBB: blood brain barrier; TTD: Therapeutic Target Database; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GEO: Gene Expression Omnibus; PPI: Protein–protein interaction; ROC: Receiver operating characteristic; AUC: area under the ROC curve; N2A-APP: Neuro-2a cell line overexpressing the Swedish mutant APP; CCK-8: Cell Counting Kit-8; AChE: acetylcholine; BChE: butyrylcholineste-rase.