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Mechanism of Dried Fruiting Bodies of Fomes officinalis Against Alzheimer's Disease: Based on Network Pharmacology and In Vitro Experimental Verification / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 173-183, 2022.
Article in Chinese | WPRIM | ID: wpr-940635
ABSTRACT
ObjectiveTo explore the possible mechanism of dried fruiting bodies of Fomes officinalis (FOA) against Alzheimer's disease (AD) based on network pharmacology and experimental verification. MethodThe effective components of FOA were retrieved from a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and previous reports. The targets of the components were searched from PharmMapper and TargetNet, and the targets related to AD from Gene Expression Omnibus (GEO), DrugBank, among other databases. Thereby, the common targets of FOA and AD were obtained, and the protein-protein interaction (PPI) network and component-target network were established based on STRING and Cytoscape 3.7.1, followed by the topology analysis of the networks, and Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the common targets. The results were verified by the molecular docking and the in vitro cell experiment. ResultA total of 24 candidate components and 242 predicted targets of FOA, and 96 common targets of FOA and AD were screened out. The key components included [2-(1-carboxyhexadecylamino)-2-aminosuccinic acid], 3-keto-dehydrosulfurenic acid, and eburicoic acid, and the active targets were albumin (ALB), acetylcholinesteraseAChE), estrogen receptor 1 (ESR1), cysteine aspartate-specific protease-3 (Caspase-3), and beta-secretase1 (BACE1). The common targets were involved in 392 GO terms, and the key terms were the β-amyloid metabolic process and cholinesterase activity. A total of 77 KEGG pathways were obtained, which mainly included estrogen signaling pathway, cholinergic synapse, and AD. The results of molecular docking showed that 7 components of FOA had high binding affinity to amyloid precursor protein (APP), BACE1, AChE, and Caspase-3. The cell survival rate rose (P<0.01) and the mRNA and protein expression of APP, BACE1, AChE, and Caspase-3 reduced in FOA groups in a dose-dependent manner compared with those in the model group (P<0.05). ConclusionThis study reveals for the first time that FOA has multi-component, multi-target, and multi-pathway characteristics in the treatment of AD, which serves as a reference for further explaining the mechanism of FOA against AD.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2022 Type: Article