AUTHOR=Pan Pengyu , Zhao Tengyu , Zhang Jian , Zhou Yuhan , Zhang Xinyue , Li Quan , Zhou Yanyan 

TITLE=Pharmacological mechanisms and therapeutic prospects of plant metabolites from traditional Chinese medicine in regulating programmed cell death in Alzheimer’s disease

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1605214

DOI=10.3389/fphar.2025.1605214

ISSN=1663-9812

ABSTRACT=Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and neuronal loss. Multiple forms of programmed cell death (PCD)—including apoptosis, pyroptosis, ferroptosis, cuproptosis, and disulfidoptosis—contribute to its pathogenesis, regulated by protein families such as caspases, RIPKs, gasdermins, and ATGs. Plant metabolites widely distributed across medicinal plants and enriched in botanical drugs used in traditional Chinese medicine (TCM), such as alkaloids, flavonoids, saponins, and polysaccharides, have attracted increasing attention for their potential regulatory effects on these PCD pathways. These metabolites are not unique to TCM, but their prevalence in TCM prescriptions provides a valuable framework for pharmacological investigation. Their biological activities are often determined by structural features—for example, the isoquinoline scaffold of berberine enhances membrane permeability, facilitating neuroprotective actions. Despite substantial research, comprehensive summaries remain limited. This review systematically integrates progress from the past 2 decades on how plant metabolites, particularly those enriched in TCM botanical drugs, regulate PCD in AD, with the aim of clarifying pharmacological mechanisms and highlighting prospects for drug discovery and clinical translation.