Beneficial effects of cyclic ether 2-butoxytetrahydrofuran from sea cucumber holothuria scabra against aβ aggregate toxicity in transgenic caenorhabditis elegans and potential chemical interaction

Journal article

Authors/Editors

NAKORN NIAMNONT

Strategic Research Themes

Publication Details

Author list: Tangrodchanapong T., Sornkaew N., Yurasakpong L., Niamnont N., Nantasenamat C., Sobhon P., Meemon K.

Publisher: MDPI

Publication year: 2021

Volume number: 26

Issue number: 8

ISSN: 1420-3049

eISSN: 1420-3049

URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105153559&doi=10.3390%2fmolecules26082195&partnerID=40&md5=9efb566b36e0060abd000515e588467b

Languages: English-Great Britain (EN-GB)

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Abstract

The pathological finding of amyloid-β (Aβ) aggregates is thought to be a leading cause of untreated Alzheimer’s disease (AD). In this study, we isolated 2-butoxytetrahydrofuran (2-BTHF), a small cyclic ether, from Holothuria scabra and demonstrated its therapeutic potential against AD through the attenuation of Aβ aggregation in a transgenic Caenorhabditis elegans model. Our results revealed that amongst the five H. scabra isolated compounds, 2-BTHF was shown to be the most effective in suppressing worm paralysis caused by Aβ toxicity and in expressing strong neuroprotec-tion in CL4176 and CL2355 strains, respectively. An immunoblot analysis showed that CL4176 and CL2006 treated with 2-BTHF showed no effect on the level of Aβ monomers but significantly reduced the toxic oligomeric form and the amount of 1,4-bis(3-carboxy-hydroxy-phenylethenyl)-benzene (X-34)-positive fibril deposits. This concurrently occurred with a reduction of reactive oxygen species (ROS) in the treated CL4176 worms. Mechanistically, heat shock factor 1 (HSF-1) (at residues histidine 63 (HIS63) and glutamine 72 (GLN72)) was shown to be 2-BTHF’s potential target that might con-tribute to an increased expression of autophagy-related genes required for the breakdown of the Aβ aggregate, thus attenuating its toxicity. In conclusion, 2-BTHF from H. scabra could protect C. elegans from Aβ toxicity by suppressing its aggregation via an HSF-1-regulated autophagic pathway and has been implicated as a potential drug for AD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

2-butoxytetrahydrofuran, Alzheimer’s disease, Amyloid-β, C. elegans, H. scabra, Sea cucumber