Neuroprotective effects of Gastrodia elata and its compounds in a Caenorhabditis elegans Alzheimer’s disease model

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-18 DOI:10.1016/j.phymed.2025.156876

Yanqing Zhang , Xiaotong Zhao , Li Gong , Changjiangsheng Lai , Jing Liu , Junbo Xie

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引用次数: 0

Abstract

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by learning and memory impairments, primarily caused by excessive β-amyloid protein (Aβ) accumulation, which induces neurotoxicity and metabolic dysfunction. Gastrodia elata (GE), a medicinal herb, has demonstrated antioxidant, antidepressant, and neuroprotective properties, making it a promising candidate for treating neurological diseases. However, systematic studies on its active compounds improving learning and memory through targeted metabolomics remain limited.

Purpose

This study aimed to evaluate the neuroprotective effects of Gastrodia elata (GE) and its active compounds, with a specific focus on learning and memory impairments in Alzheimer’s disease.

Methods

Using Caenorhabditis elegans (C. elegans) models of AD, the effects of GE and its active compounds were assessed through chemotaxis assays, targeted metabolomics, and LC-QQQ-MS analysis. Key neurotransmitter levels, including l-Leucine (l-Leu), l-Phenylalanine (l-Phe), γ-aminobutyric acid (GABA), and Acetylcholine (ACh), were quantified. The study also utilized principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to investigate metabolic biomarkers.

Results

Parishin E (BG E) was identified as the most effective compound in reducing Aβ levels and modulating key biomarkers associated with learning and memory impairments. LC-QQQ-MS analysis showed that BG E restored neurotransmitter levels closer to those of healthy controls. GE extracts (100 μg/ml) and the positive control Huperzine A (Hup A, 8 μg/ml) significantly delayed paralysis in AD C. elegans models. PCA and OPLS-DA analyses confirmed that BG E normalized metabolic biomarkers and key neurotransmitter levels associated with AD.

Conclusion

These findings highlight the therapeutic potential of Gastrodia elata, particularly its active compound Parishin E (BG E), in mitigating learning and memory impairments in Alzheimer’s disease. This study provides a foundation for further validation in advanced models and supports the development of natural therapeutics for neurological disorders.

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天麻及其化合物在秀丽隐线虫阿尔茨海默病模型中的神经保护作用

阿尔茨海默病（AD）是一种以学习和记忆障碍为特征的进行性神经退行性疾病，主要由过量的β-淀粉样蛋白（a β）积累引起，可诱导神经毒性和代谢功能障碍。天麻（GE）是一种草药，具有抗氧化、抗抑郁和神经保护作用，是治疗神经系统疾病的有希望的候选者。然而，通过靶向代谢组学对其活性成分改善学习和记忆的系统研究仍然有限。目的研究天麻及其活性成分对阿尔茨海默病学习记忆损伤的神经保护作用。方法采用秀丽隐杆线虫（C. elegans） AD模型，通过趋化性实验、靶向代谢组学和LC-QQQ-MS分析评估GE及其活性化合物对AD的影响。定量测定l-亮氨酸（l-Leu）、l-苯丙氨酸（l-Phe）、γ-氨基丁酸（GABA）和乙酰胆碱（ACh）等关键神经递质水平。该研究还利用主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）来研究代谢生物标志物。结果bbg E在降低学习和记忆障碍相关的Aβ水平和调节关键生物标志物方面最为有效。LC-QQQ-MS分析显示BG E恢复的神经递质水平更接近健康对照组。GE提取物（100 μg/ml）和阳性对照石杉碱A （Hup A, 8 μg/ml）可显著延缓线虫模型的麻痹。PCA和OPLS-DA分析证实BG E使与AD相关的代谢生物标志物和关键神经递质水平正常化。结论天麻具有明显的治疗阿尔茨海默病的作用，特别是其活性成分Parishin E （BG E）具有减轻阿尔茨海默病学习记忆障碍的作用。该研究为进一步验证先进模型奠定了基础，并支持了神经疾病自然疗法的发展。

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.