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Published VersionCC BY-NC-ND V4.0, Open Access
Journal article
Triterpenoid saponin-containing Holothuria leucospilota extract mitigates amyloid-βr proteotoxicity in transgenic C. elegans through activations of protein clearance and stress resistance pathways
Food Bioscience, Vol.77, pp.1-19
2026
Abstract
The black sea cucumber Holothuria leucospilota, an Asian traditional food and medicine, has been explored for health benefits, including neuroprotective effects. Although its anti-Parkinson's effects have been demonstrated, its potential anti-Alzheimer's effects remain unexplored. Therefore, this study aimed to investigate the effects and underlying mechanisms of H. leucospilota extracts on amyloid-(3 (A(3) proteotoxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD). All fractions of H. leucospilota extracts were proven to be non-toxic to C. elegans. Among them, the ethyl acetate fraction (HLEA) at 500 mu g/mL exhibited the greatest efficacy due to its ability to delay A(3-induced paralysis in muscular A(3-expressing C. elegans. Moreover, HLEA at 500 mu g/mL rescued the chemotaxis defects in neuronal A(3-expressing worms. The levels of A(3 oligomers and deposits declined after HLEA treatment of AD worms. Correspondingly, HLEA alleviated A(3 toxicity by lowering ROS levels and extending the lifespan of AD worms. Furthermore, differential RNA sequencing analysis revealed that the lysosome, proteasome, and antioxidant pathways were activated in HLEA-treated AD worms. RT-qPCR assays confirmed that HLEA upregulated ubiquitin-proteasome system, autophago-lysosomal, and antioxidant genes. Moreover, HLEA treatment promoted the nuclear localization of key transcription factors, SKN-1 and DAF-16, along with upregulation of their downstream antioxidant genes, indicating activation of SKN-1 and DAF-16 signaling pathways. Lastly, mass spectrometry analysis revealed that HLEA was predominantly composed of triterpenoid saponins. In summary, HLEA at 500 mu g/mL diminished A(3 proteotoxicity by activating the protein clearance mechanism and SKN-1 and DAF-16 stress resistance pathways in the C. elegans AD model.
Details
- Title
- Triterpenoid saponin-containing Holothuria leucospilota extract mitigates amyloid-βr proteotoxicity in transgenic C. elegans through activations of protein clearance and stress resistance pathways
- Authors
- Salinthip Thongdechsri - Mahidol UniversityChanathip Kamonnat - Mahidol UniversityTanatcha Sanguanphun - Mahidol UniversityPichnaree Kraokaew - Mahidol UniversityPrapaporn Jattujan - Khon Kaen UniversityNakorn Niamnont - King Mongkut's University of Technology ThonburiStuart J. Smith - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringScott F. Cummins - University of the Sunshine Coast, Queensland, School of Science, Technology and EngineeringNopporn Jongkamonwiwat - Mahidol UniversityPrasert Sobhon - Mahidol UniversityKrai Meemon (Corresponding Author) - Mahidol University
- Publication details
- Food Bioscience, Vol.77, pp.1-19
- Publisher
- Elsevier BV
- Date published
- 2026
- DOI
- 10.1016/j.fbio.2026.108427
- ISSN
- 2212-4306; 2212-4292
- Copyright note
- © 2026 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
- Data Availability
- Data will be made available on request.
- Grant note
- This study was funded by National Research Council of Thailand (NRCT) and Mahidol University (N42A660511) and partially supported by the Central Instrument Facility (CIF) grant from Faculty of Science, Mahidol University.
- Organisation Unit
- School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991212664502621
- Output Type
- Journal article
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