A network pharmacology approach to uncover the key ingredients in Ginkgo Folium and their anti-Alzheimer’s disease mechanisms

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.