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Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives

Neural stem cells (NSCs) differentiate into multiple cell types, including neurons, astrocytes, and oligodendrocytes, and provide an excellent platform to screen drugs against neurodegenerative diseases. Flavonoids exert a wide range of biological functions on several cell types and affect the fate...

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Autores principales: Lee, Ha-Rim, Kang, Jin Mi, Kim, Young Min, Kim, Sagang, Ann, Jihyae, Lee, Jeewoo, Kim, Hyun-Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995541/
https://www.ncbi.nlm.nih.gov/pubmed/31810286
http://dx.doi.org/10.3390/biom9120812
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author Lee, Ha-Rim
Kang, Jin Mi
Kim, Young Min
Kim, Sagang
Ann, Jihyae
Lee, Jeewoo
Kim, Hyun-Jung
author_facet Lee, Ha-Rim
Kang, Jin Mi
Kim, Young Min
Kim, Sagang
Ann, Jihyae
Lee, Jeewoo
Kim, Hyun-Jung
author_sort Lee, Ha-Rim
collection PubMed
description Neural stem cells (NSCs) differentiate into multiple cell types, including neurons, astrocytes, and oligodendrocytes, and provide an excellent platform to screen drugs against neurodegenerative diseases. Flavonoids exert a wide range of biological functions on several cell types and affect the fate of NSCs. In the present study, we investigated whether the structure-activity relationships of flavone derivatives influence NSC differentiation. As previously reported, we observed that PD98059 (2′-amino-3′-methoxy-flavone), compound 2 (3′-methoxy-flavone) induced astrocytogenesis. In the present study, we showed that compound 3 (2′-hydroxy-3′-methoxy-flavone), containing a 3′-methoxy group, and a non-bulky group at C2′ and C4′, induced astrocytogenesis through JAK-STAT3 signaling pathway. However, compound 1 and 7–12 without the methoxy group did not show such effects. Interestingly, the compounds 4 (2′,3′-dimethoxyflavone), 5 (2′-N-phenylacetamido-3′-methoxy-flavone), and 6 (3′,4′-dimethoxyflavone) containing 3′-methoxy could not promote astrocytic differentiation, suggesting that both the methoxy groups at C3′ and non-bulky group at C2′ and C4′ are required for the induction of astrocytogenesis. Notably, compound 6 promoted neuronal differentiation, whereas its 4′-demethoxylated analog, compound 2, repressed neurogenesis, suggesting an essential role of the methoxy group at C4′ in neurogenesis. These findings revealed that subtle structural changes of flavone derivatives have pronounced effects on NSC differentiation and can guide to design and develop novel flavone chemicals targeting NSCs fate regulation.
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spelling pubmed-69955412020-02-13 Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives Lee, Ha-Rim Kang, Jin Mi Kim, Young Min Kim, Sagang Ann, Jihyae Lee, Jeewoo Kim, Hyun-Jung Biomolecules Article Neural stem cells (NSCs) differentiate into multiple cell types, including neurons, astrocytes, and oligodendrocytes, and provide an excellent platform to screen drugs against neurodegenerative diseases. Flavonoids exert a wide range of biological functions on several cell types and affect the fate of NSCs. In the present study, we investigated whether the structure-activity relationships of flavone derivatives influence NSC differentiation. As previously reported, we observed that PD98059 (2′-amino-3′-methoxy-flavone), compound 2 (3′-methoxy-flavone) induced astrocytogenesis. In the present study, we showed that compound 3 (2′-hydroxy-3′-methoxy-flavone), containing a 3′-methoxy group, and a non-bulky group at C2′ and C4′, induced astrocytogenesis through JAK-STAT3 signaling pathway. However, compound 1 and 7–12 without the methoxy group did not show such effects. Interestingly, the compounds 4 (2′,3′-dimethoxyflavone), 5 (2′-N-phenylacetamido-3′-methoxy-flavone), and 6 (3′,4′-dimethoxyflavone) containing 3′-methoxy could not promote astrocytic differentiation, suggesting that both the methoxy groups at C3′ and non-bulky group at C2′ and C4′ are required for the induction of astrocytogenesis. Notably, compound 6 promoted neuronal differentiation, whereas its 4′-demethoxylated analog, compound 2, repressed neurogenesis, suggesting an essential role of the methoxy group at C4′ in neurogenesis. These findings revealed that subtle structural changes of flavone derivatives have pronounced effects on NSC differentiation and can guide to design and develop novel flavone chemicals targeting NSCs fate regulation. MDPI 2019-12-02 /pmc/articles/PMC6995541/ /pubmed/31810286 http://dx.doi.org/10.3390/biom9120812 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Ha-Rim
Kang, Jin Mi
Kim, Young Min
Kim, Sagang
Ann, Jihyae
Lee, Jeewoo
Kim, Hyun-Jung
Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives
title Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives
title_full Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives
title_fullStr Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives
title_full_unstemmed Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives
title_short Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives
title_sort functional group-dependent induction of astrocytogenesis and neurogenesis by flavone derivatives
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995541/
https://www.ncbi.nlm.nih.gov/pubmed/31810286
http://dx.doi.org/10.3390/biom9120812
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