Die Pharmazie · 2026
Investigating the Therapeutic Mechanism of Ginkgo Biloba Extract in Alzheimer's Disease via Integrated Network Pharmacology and Molecular Docking.
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Li Yipei, Gong Juan, Yang Liu, Jin Li, Peng Ruirui, Wang Fang, Wang Li
Аннотация
OBJECTIVE: This study aimed to investigate the mechanisms through which ginkgolides in Ginkgo biloba extract (GBE) may protect against Alzheimer's disease (AD).
METHODS: Candidate ginkgolide constituents and their putative targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. AD-associated genes were retrieved from OMIM and GeneCards. Overlapping targets were used to construct component-target-disease and protein-protein interaction (PPI) networks for hub target screening. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVID. AutoDock Vina was used for molecular docking, and molecular dynamics simulations were conducted to evaluate ligand-target stability. The predicted mechanisms were further examined in APP/PS1 mice and Aβ1-42-treated HT22 cells.
RESULTS: A total of 27 active ginkgolide-related constituents and 336 intersecting targets were identified. Ginkgolides B and M were identified as the major active compounds, whereas MAPK3, HIF-1α, and AKT1 emerged as important targets. Enrichment analysis indicated a close association with the PI3K-Akt pathway. Docking analysis showed that ginkgolides B and M bound strongly to MAPK3 and HIF-1α with binding energies ranging from -9.34 to -8.41 kcal/mol. Molecular dynamics simulations supported the stable formation of these complexes. In vivo and in vitro experiments showed that ginkgolides B and M alleviated synaptic protein damage, decreased HIF-1α expression, and improved cognitive deficits.
CONCLUSIONS: Ginkgolides B and M may contribute to anti-AD effects in experimental models, partly through modulation of HIF-1α-related stress responses and PI3K-Akt-associated survival pathways.
METHODS: Candidate ginkgolide constituents and their putative targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. AD-associated genes were retrieved from OMIM and GeneCards. Overlapping targets were used to construct component-target-disease and protein-protein interaction (PPI) networks for hub target screening. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVID. AutoDock Vina was used for molecular docking, and molecular dynamics simulations were conducted to evaluate ligand-target stability. The predicted mechanisms were further examined in APP/PS1 mice and Aβ1-42-treated HT22 cells.
RESULTS: A total of 27 active ginkgolide-related constituents and 336 intersecting targets were identified. Ginkgolides B and M were identified as the major active compounds, whereas MAPK3, HIF-1α, and AKT1 emerged as important targets. Enrichment analysis indicated a close association with the PI3K-Akt pathway. Docking analysis showed that ginkgolides B and M bound strongly to MAPK3 and HIF-1α with binding energies ranging from -9.34 to -8.41 kcal/mol. Molecular dynamics simulations supported the stable formation of these complexes. In vivo and in vitro experiments showed that ginkgolides B and M alleviated synaptic protein damage, decreased HIF-1α expression, and improved cognitive deficits.
CONCLUSIONS: Ginkgolides B and M may contribute to anti-AD effects in experimental models, partly through modulation of HIF-1α-related stress responses and PI3K-Akt-associated survival pathways.