Abstract
Background: Chlorogenic acid (CGA), a polyphenolic substance extracted from many traditional Chinese medicines, exerts a mitigative effect in dementia, including Alzheimer’s disease (AD). However, the pathological mechanisms of CGA against AD remain obscure.
Objective: To elucidate the core targets, functional characteristics, and underlying mechanisms of CGA against AD using network pharmacology approaches and molecular docking technologies.
Methods: GEO database was used to identify the differentially expressed genes (DEGs) in AD. PharmMpper, TargetNet, and SwissTargetPrediction predicted the CGA-related targets. STRING and Cytoscape were employed to construct and analyze the PPI network. Moreover, the Metascape platform was used to perform the GO biological processes and KEGG pathways enrichment. Molecular docking was performed using Autodock Vina software.
Results: A total of 5437 targets related to AD were identified with |log2Fold Change (FC)| ≥ 1 and P < 0.05. Based on public databases, 193 putative target genes of CGA were screened. Using the Venn diagram, we found 137 co-targets between CGA and AD. According to the PPI network, 23 core targets for CGA to treat AD were obtained. KEGG enrichment displayed that the PI3K-Akt signaling pathway, MAPK signaling pathway, apoptosis, and NOD-like receptor signaling pathway were several important signaling pathways involved in CGA against AD. SRC, EGFR, HSP90AA1, MAPK1, RHOA, and PIK3R1 were hub targets associated with the activities of CGA against AD. Molecular docking analysis revealed a good binding affinity between CGA and these targets through hydrogen bonds.
Conclusion: CGA might exert therapeutic effects in AD by regulating multiple targets and signaling pathways. However, further in vitro and in vivo experiments are required to thoroughly confirm the detailed targets and mechanisms of CGA against AD.
Keywords: Network pharmacology, chlorogenic acid, Alzheimer’s disease, therapeutic targets, molecular docking, receptor.
Graphical Abstract
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