ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition, Psychology and Brain Health
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1683852
This article is part of the Research TopicThe Foundational Components and Elements of Plant Foods for Neurological Nutrition and Well-beingView all 9 articles
Exploring the Molecular Mechanisms of Pueraria in Alzheimer's Disease Treatment Using Machine Learning and Network Pharmacology
Provisionally accepted
- 1Second Affiliated Hospital of Wannan Medical College, Wuhu, China
- 2Yijishan Hospital of Wannan Medical College, Wuhu, China
- 3Wuhu Third People's Hospital, Wu Hu, China
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Abstract: Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder, characterized by amyloid-β deposition, tau pathology, neuroinflammation, and metabolic dysfunction. While conventional treatments have been widely studied, food-based interventions are emerging as potential neuroprotective strategies. Pueraria, a nutrient-rich food, has shown promise in promoting brain health, but its mechanisms in AD prevention and management remain insufficiently understood. Methods: In this study, we utilized network pharmacology, transcriptomics, and machine learning to investigate the neuroprotective effects of Pueraria. Through analysis of five transcriptomic datasets (GSE5281, GSE29378, GSE36980, GSE37263, and GSE138260), we identified genes associated with AD and screened 15 active compounds from Pueraria lobata using HERB and TCMSP databases. Machine learning models prioritized key targets, and molecular docking simulations assessed the binding affinities of Pueraria compounds to these targets. In vivo validation was performed in AD model mice to evaluate the cognitive-enhancing effects of Pueraria. Results: We identified 45 overlapping targets between Pueraria and AD, primarily related to synaptic plasticity and 3 neurotransmission. Among these, PFKFB3 emerged as a key mediator of Pueraria's neuroprotective effects. Molecular docking confirmed strong binding affinities between Pueraria compounds and PFKFB3, supporting their functional role. Experimental data showed that Pueraria improved cognitive function in AD mice, underscoring its potential as a neuroprotective agent. Conclusion: This study highlights Pueraria as a promising functional food for AD prevention and management, emphasizing the potential of plant-based dietary interventions for brain health. Our findings provide a basis for further exploration of food-derived neuroprotective strategies.
Keywords: Pueraria, Alzheimer's disease, Network Pharmacology, machine learning, Neuroprotection
Received: 11 Aug 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Ye, Li, Guan, Qin, Xu, Wu, Huang and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Junjie Gao, wnmcjykjj@163.com
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