Protective effect of Gastrodia elata Blume in a Caenorhabditis elegans model of Alzheimer's disease based on network pharmacology

Abstract

The aim of the present study was to investigate the protective effect of Gastrodia elata Blume (GEB) against Caenorhabditis elegans ( C. elegans ) in Alzheimer's disease (AD) through network pharmacology. Firstly, the active constituents of GEB through ETCM and BATMAN-TCM databases were collected and its potential AD-related targets in Swiss Target Prediction were predicted. The potential targets related to AD were collected from the GeneCards, OMIM, CTD and DisGeNET databases, and the differential genes (DEGs) between the normal population and the AD patient population in GSE5281 chip of the Gene Expression Omnibus database were collected at the same time. The intersection of the three targets yielded 59 key targets of GEB for the treatment of AD. The drug-active ingredient-target-AD network diagram was constructed and visualized with Cytoscape software to obtain the core components. Subsequently, protein-protein interaction analysis (PPI) was performed on 59 key targets through STRING database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses was performed on 59 key targets. Finally, molecular docking was conducted between core components and core targets using AutoDock software, and the C. elegans AD model was used for experimental verification to explore the regulatory paralysis effect of core components on the C. elegans model, β-amyloid (Aβ) plaque deposition, and quantitative polymerase chain reaction verification of the regulatory effect of components on targets. The GEB components 4,4'-dihydroxydiphenyl methane (DM) and protocatechuic aldehyde (PA) were found to be most strongly associated with AD, and five core targets were identified in the PPI network, including GAPDH, EP300, HSP90AB1, KDM6B, and CREBBP. In addition to GAPDH, the other four targets were successfully docked with DM and PA using AutoDock software. Compared with the control group, 0.5 mM DM and 0.25 mM PA significantly delayed C. elegans paralysis (P<0.01), and inhibited the aggregation of Aβ plaques in C. elegans . Both DM and PA could upregulate the expression level of core target gene HSP90AB1 (P<0.01), and DM upregulated the expression of KDM6B (P<0.01), suggesting that DM and PA may be potential active components of GEB in the treatment of AD.

Procatechuic acid and protocatechuic aldehyde increase survival of Caenorhabditis elegans after fungal infection and inhibit fungal virulence

“…Previous reports have indicated that treatment with PCA was helpful for nematodes against heat stress, osmotic stress, and oxidative stress ( Kim et al, 2014 ; Schmitt et al, 2021 ). In addition, treatment with PAL could delay paralysis and inhibit aggregation of Aβ plaques, suggesting its neuroprotective effect ( Shi et al, 2023 ). We found that treatment with both 10–100 μM PCA and 10–100 μM PAL inhibited adverse effect of SC5314 infection in decreasing lifespan ( Figure 1 ).…”

Changes in Soil Chemistry and Microbial Communities in Rhizospheres of Planted Gastrodia elata on a Barren Slope and under a Forest

“…G. elata is a very important medicinal orchid with documented therapeutic properties [3][4][5][7][8][9][10]. It is, therefore, essential to improve its production.…”

“…[3,6]. Pharmacological studies have shown that the plant has a neuroprotective ability and may represent an essential resource for the treatment of chronic diseases, including Alzheimer's, epilepsy, dementia, brain aging-related diseases, hypertension, depression, and for the improvement of blood flow in the brain and heart [7][8][9][10][11]. Accordingly, the demand for high-quality G. elata is increasing, and the reliance on wild G. elata from mountainous regions is leading to its scarcity and an inability to meet market demand [6,11].…”

4,4′-methylenediphenol reduces Aβ-induced toxicity in a Caenorhabditis elegans model of Alzheimer’s disease

“…Gastrodia elata is a well-known and valuable medicinal herb with a distinctive odor that is suitable for growing in moist and well-ventilated shady environments, such as Yunnan and Guizhou in China. Studies have shown that Gastrodia elata and its extracts have potential for use in the prevention and treatment of AD ( Shi et al, 2023a ). Indeed, one of the active ingredients of Gastrodia elata , p-hydroxybenzyl alcohol, was reported to ameliorate Aβ-induced toxic effects ( Liu et al, 2022 ).…”