Screening of Active Substances Regulating Alzheimer's Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets

Yecan Pan; Zishu Li; Xiaoyu Zhao; Yang Du; Lin Zhang; Yushun Lu; Ling Yang; Yilin Cao; Jing Qiu; Yongzhong Qian

doi:10.3390/foods13040612

Screening of Active Substances Regulating Alzheimer's Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets

Foods. 2024 Feb 18;13(4):612. doi: 10.3390/foods13040612.

Authors

Yecan Pan^{1

2}, Zishu Li^{1

2}, Xiaoyu Zhao^{1

2}, Yang Du^{1

2}, Lin Zhang^{1

2}, Yushun Lu^{1

2}, Ling Yang^{1

2}, Yilin Cao^{1

2}, Jing Qiu^{1

2}, Yongzhong Qian^{1

2}

Affiliations

¹ Key Laboratory of Agro-Product Quality and Safety, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
² Key Laboratory of Agri-Food Quality and Safety, Ministry of Agriculture and Rural Affairs, Beijing 100081, China.

Abstract

Ginger has been reported to potentially treat Alzheimer's disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger's active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger's active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient-key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein-protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.

Keywords: 6-Gingerol; Alzheimer’s disease (AD); ginger; molecular dynamics (MD); network pharmacology.

Abstract

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