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Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239

Alzheimer’s disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-β (Aβ) peptide plays a key role in AD pathogenesis in what is known as the Aβ cascade hypothesis. This hypothesis suggests the importance of suppressing Aβ aggrega...

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Autores principales: Fujihara, Koji, Hashimoto, Takumi, Sasaki, Hiroaki, Koyama, Kiyotaka, Kinoshita, Kaoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088752/
https://www.ncbi.nlm.nih.gov/pubmed/37038034
http://dx.doi.org/10.1007/s11418-023-01696-9
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author Fujihara, Koji
Hashimoto, Takumi
Sasaki, Hiroaki
Koyama, Kiyotaka
Kinoshita, Kaoru
author_facet Fujihara, Koji
Hashimoto, Takumi
Sasaki, Hiroaki
Koyama, Kiyotaka
Kinoshita, Kaoru
author_sort Fujihara, Koji
collection PubMed
description Alzheimer’s disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-β (Aβ) peptide plays a key role in AD pathogenesis in what is known as the Aβ cascade hypothesis. This hypothesis suggests the importance of suppressing Aβ aggregation and Aβ production. The latter process is governed by β-site APP Cleaving Enzyme1 (BACE1) and γ-secretase. We, therefore, focused on Aβ aggregation inhibitory activity, initially assessing numerous extracts derived from our marine-derived fungus collections. One EtOAc extract derived from an Aspergillus sp. exhibited Aβ aggregation inhibitory activity. Eleven known compounds (1–11) were isolated from CHCl(3) and EtOAc extracts derived from the fungus, and the structures were identified based on MS, NMR, and ECD spectra. Compounds 2, 6, and 10 inhibited Aβ aggregation with IC(50) values of 2.8, 3.9, and 8.1 μM, respectively. The protective effect on SH-SY5Y cells against Aβ toxicity was also evaluated, and compounds 6 and 10 significantly alleviated Aβ toxicity. BACE1 inhibitory activity was also examined, and compounds 4, 5, 7, 10, and 11 inhibited BACE1 activity with IC(50) values of 14.9, 70.0, 36.5, 28.0, and 72.8 μM, respectively. These data suggest that compound 10 could be useful in AD treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11418-023-01696-9.
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spelling pubmed-100887522023-04-12 Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239 Fujihara, Koji Hashimoto, Takumi Sasaki, Hiroaki Koyama, Kiyotaka Kinoshita, Kaoru J Nat Med Original Paper Alzheimer’s disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-β (Aβ) peptide plays a key role in AD pathogenesis in what is known as the Aβ cascade hypothesis. This hypothesis suggests the importance of suppressing Aβ aggregation and Aβ production. The latter process is governed by β-site APP Cleaving Enzyme1 (BACE1) and γ-secretase. We, therefore, focused on Aβ aggregation inhibitory activity, initially assessing numerous extracts derived from our marine-derived fungus collections. One EtOAc extract derived from an Aspergillus sp. exhibited Aβ aggregation inhibitory activity. Eleven known compounds (1–11) were isolated from CHCl(3) and EtOAc extracts derived from the fungus, and the structures were identified based on MS, NMR, and ECD spectra. Compounds 2, 6, and 10 inhibited Aβ aggregation with IC(50) values of 2.8, 3.9, and 8.1 μM, respectively. The protective effect on SH-SY5Y cells against Aβ toxicity was also evaluated, and compounds 6 and 10 significantly alleviated Aβ toxicity. BACE1 inhibitory activity was also examined, and compounds 4, 5, 7, 10, and 11 inhibited BACE1 activity with IC(50) values of 14.9, 70.0, 36.5, 28.0, and 72.8 μM, respectively. These data suggest that compound 10 could be useful in AD treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11418-023-01696-9. Springer Nature Singapore 2023-04-10 2023 /pmc/articles/PMC10088752/ /pubmed/37038034 http://dx.doi.org/10.1007/s11418-023-01696-9 Text en © The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Paper
Fujihara, Koji
Hashimoto, Takumi
Sasaki, Hiroaki
Koyama, Kiyotaka
Kinoshita, Kaoru
Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239
title Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239
title_full Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239
title_fullStr Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239
title_full_unstemmed Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239
title_short Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239
title_sort inhibition of aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, aspergillus sp. mpuc239
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088752/
https://www.ncbi.nlm.nih.gov/pubmed/37038034
http://dx.doi.org/10.1007/s11418-023-01696-9
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