Plant-derived natural products modulate astrocyte function: Therapeutic strategies for Alzheimer's disease. 2025

Huayuan Wei, and Guangming Zhang, and Xu Yan, and Anliu Zhao, and Yujia Zheng, and Yang Shao, and Lin Yang, and Jie Wang, and Xijuan Jiang
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

BACKGROUND Alzheimer's disease (AD) is a gradually worsening neurodegenerative condition with limited treatment options, highlighting the need for novel therapies. Astrocytes play key roles in AD pathogenesis. Natural products show promise for treating AD through modulating amyloid-beta (Aβ) and tau pathology, inhibiting neuroinflammation and oxidative stress, and protecting cellular organelles. Preclinical evidence supports their efficacy in targeting astrocyte-related mechanisms, enhancing cognition, and reducing neuronal damage. OBJECTIVE Systematically summarize and evaluate the medicinal benefits of plant-derived natural products in modulating astrocyte-mediated processes to attenuate AD progression. METHODS A comprehensive literature review was performed in PubMed and Web of Science, utilizing targeted keywords such as "natural products", "active compounds", "Alzheimer's disease", and "astrocytes". The review primarily focused on studies published between 2013 and 2024, with the selected literature systematically categorized and analyzed. RESULTS This review highlights the medicinal benefits of plant-derived natural products, such as flavonoids, alkaloids, polyphenols, and terpenes in targeting astrocyte morphology and function to combat AD. These bioactive compounds modulate key pathological processes, including neuroinflammation, oxidative stress, Aβ metabolism, tau hyperphosphorylation, mitochondrial dysfunction, and ER stress, outlining pathways to alleviate AD through astrocytic effects. The review also summarizes clinical progress and major challenges in translating these compounds, such as variability, low bioavailability, and delivery limitations. CONCLUSIONS This study addresses a critical gap by systematically elucidating the relationship between astrocytes and AD, and therapeutic potential of plant-derived natural products. It aims to expand treatment options for patients and advance the development of therapeutic strategies in the field of AD management.

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