Exploring the mechanism of Crataegus pinnatifida fruit flavonoids to improve Alzheimer’s disease based on network pharmacology and molecular docking

Abstract

This study aims to explore the mechanism by which flavonoids in Crataegus pinnatifida fruit improve Alzheimer’s disease (AD) through network pharmacology and molecular docking technology. The flavonoid components present in Crataegus pinnatifida fruit were gathered from the HERB, HIT, and ETCM databases, and were further supplemented by relevant published literature. The PubChem and SwissTargetPrediction databases were utilized to predict potential targets, and a “Crataegus pinnatifida fruit-active ingredient-target” network was constructed using Cytoscape 3.9.0 software. The GeneCards database was utilized to identify targets associated with AD, which were subsequently intersected with the active targets of Crataegus pinnatifida fruit. A protein-protein interaction (PPI) network was constructed using the STRING platform. KEGG enrichment analysis of the core targets was conducted on an online bioinformatics mapping platform, while molecular docking of the primary active components and core targets was executed using AutoDock software. Eight flavonoids and 160 potential targets were identified from Crataegus pinnatifida fruit, of which 147 targets were linked to AD. The results of the “Crataegus pinnatifida fruit-active ingredient-target” network indicated that quercetin was the principal flavonoid active ingredient. PPI analysis revealed that SRC and EGFR were the key targets, and KEGG analysis identified the main enrichment pathways as Pathways in cancer, PI3K/Akt signaling pathway, and Proteoglycans in cancer. Molecular docking confirmed the strong binding affinity between the core targets and the primary active ingredient. The interaction of quercetin with the key targets SRC and EGFR may represent a significant mechanism by which flavonoids from Crataegus pinnatifida fruit contribute to the improvement of AD.

Keywords

Crataegus pinnatifida fruit / flavonoids / Alzheimer’s disease / network pharmacology / molecular docking

Acknowledgements

This research was supported by National Natural Science Foundation of China (No. 82374333, No.82173961), LiaoNing Revitalization Talents Program (XLYC2203200), SPU Excellent Youth Program (YQ202310), SPU Youth Career Development plan (ZQN202211), Key Laboratory of polysaccharide bioactivity evaluation of TCM of Liaoning Province-Liaoning Distinguished Professor Project for Ying Jia (2017), High-level innovation and entrepreneurship team of Liaoning Province (XLYC2008029), Liaoning Provincial Department of Education Fund (LJ212410163006, LJ212410163018), Postgraduate Education and Teaching Reform Research Project of Liaoning Province in 2024 (LNYJG2024251).

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