Phytochemicals as modulators of Astrocytes in Alzheimer's disease: A therapeutic perspective.

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-09-28 DOI:10.1016/j.phymed.2025.157347

Shaojun Wang, Zhigang Zhang, Yilin Liu, Songlan Gao, Lin Wang, Jun Yang, Yu Wang

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引用次数: 0

Abstract

Background: Astrocytes play a crucial role in Alzheimer's disease (AD) pathogenesis, contributing to inflammation, amyloid plaque formation, and disease progression, making them promising therapeutic targets. Despite extensive research, the mechanisms underlying astrocytic dysfunction in AD and their modulation by phytochemicals remain incompletely understood, representing a critical gap in current knowledge.

Purpose: This review aims to elucidate the pathological mechanisms involving astrocytes in AD and evaluate the therapeutic potential of phytochemicals in modulating astrocytic activity.

Methods: We systematically analysed recent studies on astrocytic activation, target receptors, and signalling pathways in AD and their regulation by phytochemicals. The studies were identified through searches of databases including PubMed, Web of Science, ScienceDirect, and Google Scholar.

Results: Our findings reveal that abnormal activation of astrocytic receptors and downstream signaling pathways, such as RAGE/NF-κB, ERK/c-fos/NFATc1, AKT/Nrf2/NF-κB, and PI3K/Akt/GSK-3β, disrupt immune homeostasis in AD models. Phytochemicals, including tanshinone IIA, honokiol, aucubin, cornuside, luteolin, naringenin, daphnetin, and gelsemine, show promising effects in delaying AD progression. These effects are mediated through multiple mechanisms, such as inhibiting pro-inflammatory pathways, enhancing anti-inflammatory responses, promoting Aβ clearance, stimulating synaptogenesis, regulating neurotrophic factors, and reducing oxidative stress. These findings highlight the pivotal role of astrocytes in AD pathophysiology and the potential of phytochemicals to modulate astrocytic dysfunction.

Conclusions: By providing a comprehensive overview of astrocytic mechanisms and therapeutic interventions, this review offers a theoretical foundation for developing phytochemical-based strategies in AD therapy and underscores the need for further preclinical and clinical investigations to translate these findings into practical treatments.

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植物化学物质作为阿尔茨海默病星形胶质细胞的调节剂：治疗观点。

背景：星形胶质细胞在阿尔茨海默病（AD）的发病机制中起着至关重要的作用，有助于炎症、淀粉样斑块形成和疾病进展，使其成为有希望的治疗靶点。尽管进行了广泛的研究，但阿尔茨海默病星形细胞功能障碍的机制及其由植物化学物质调节的机制仍然不完全清楚，这代表了当前知识的一个关键空白。目的：本文旨在阐明星形细胞在阿尔茨海默病中的病理机制，并评价植物化学物质调节星形细胞活性的治疗潜力。方法：系统分析了近年来有关AD星形细胞活化、靶受体、信号通路及植物化学物质调控的研究进展。这些研究是通过检索PubMed、Web of Science、ScienceDirect和b谷歌Scholar等数据库确定的。结果：我们的研究结果表明，星形细胞受体和下游信号通路如RAGE/NF-κB、ERK/c-fos/NFATc1、AKT/Nrf2/NF-κB和PI3K/ AKT/ GSK-3β的异常激活，破坏了AD模型的免疫稳态。植物化学物质，包括丹参酮IIA、檀香醇、桃红素、山茱萸苷、木犀草素、柚皮素、瑞香素和明胶，在延缓AD进展方面显示出有希望的效果。这些作用是通过多种机制介导的，如抑制促炎途径、增强抗炎反应、促进Aβ清除、刺激突触发生、调节神经营养因子和减少氧化应激。这些发现强调了星形胶质细胞在阿尔茨海默病病理生理中的关键作用，以及植物化学物质调节星形胶质细胞功能障碍的潜力。结论：通过对星形细胞形成机制和治疗干预措施的全面概述，本综述为开发基于植物化学的AD治疗策略提供了理论基础，并强调了进一步的临床前和临床研究将这些发现转化为实际治疗的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.