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

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.

Keywords: Alzheimer’s disease; Caenorhabditis elegans; Gastrodia elata; Parishin E; Targeted metabolomics.