Ameliorative effect of Luffa cylindrica fruits on Caenorhabditis elegans and cellular models of Alzheimer's disease-related pathology via autophagy induction.
Phytother Res
; 37(10): 4639-4654, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-37394882
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored.AIMS:
This study was conducted with the goal of identifying potential anti-AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD-like models and exploring their mechanisms of action. MATERIALS &METHODS:
Our laboratory's in-house herbal extract library was utilized to screen for potential anti-AD candidates using the C. elegans AD-like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD-like models, specifically targeting Aß- and Tau-induced pathology. In vitro validation was conducted using PC-12 cells. To investigate the role of autophagy in mediating the anti-AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed.RESULTS:
The ethanol extract of air-dried fruits of Luffa cylindrica (LCE), a medicine-food homology species, was found to inhibit Aß- and Tau-induced pathology (paralysis, ROS production, neurotoxicity, and Aß and pTau deposition) in C. elegans AD-like models. LCE was non-toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti-AD efficacy is weakened with the RNAi knockdown of autophagy-related genes. Additionally, LCE induced mTOR-mediated autophagy, reduced the expression of AD-associated proteins, and decreased cell death in PC-12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3-methyladenine).DISCUSSION:
LCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD-like models. RNAi knockdown of autophagy-related genes and cotreatment with autophagy inhibitors weakened its anti-AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE.CONCLUSION:
Our findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Neuroprotetores
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Luffa
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Proteínas de Caenorhabditis elegans
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Phytother Res
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2023
Tipo de documento:
Article