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4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo
Although 4-O-Methylhonokiol (MH) effects on neuronal and immune cells have been established, it is still unclear whether MH can cause a change in the structure and function of the cardiovascular system. The overarching goal of this study was to evaluate the effects of MH, isolated from Magnolia gran...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384692/ https://www.ncbi.nlm.nih.gov/pubmed/30699965 http://dx.doi.org/10.3390/molecules24030475 |
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author | Singha, Santu K. Muhammad, Ilias Ibrahim, Mohamed Ali Wang, Mei Ashpole, Nicole M. Shariat-Madar, Zia |
author_facet | Singha, Santu K. Muhammad, Ilias Ibrahim, Mohamed Ali Wang, Mei Ashpole, Nicole M. Shariat-Madar, Zia |
author_sort | Singha, Santu K. |
collection | PubMed |
description | Although 4-O-Methylhonokiol (MH) effects on neuronal and immune cells have been established, it is still unclear whether MH can cause a change in the structure and function of the cardiovascular system. The overarching goal of this study was to evaluate the effects of MH, isolated from Magnolia grandiflora, on the development of the heart and vasculature in a Japanese medaka model in vivo to predict human health risks. We analyzed the toxicity of MH in different life-stages of medaka embryos. MH uptake into medaka embryos was quantified. The LC(50) of two different exposure windows (stages 9–36 (0–6 days post fertilization (dpf)) and 25–36 (2–6 dpf)) were 5.3 ± 0.1 μM and 9.9 ± 0.2 μM. Survival, deformities, days to hatch, and larval locomotor response were quantified. Wnt 1 was overexpressed in MH-treated embryos indicating deregulation of the Wnt signaling pathway, which was associated with spinal and cardiac ventricle deformities. Overexpression of major proinflammatory mediators and biomarkers of the heart were detected. Our results indicated that the differential sensitivity of MH in the embryos was developmental stage-specific. Furthermore, this study demonstrated that certain molecules can serve as promising markers at the transcriptional and phenotypical levels, responding to absorption of MH in the developing embryo. |
format | Online Article Text |
id | pubmed-6384692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63846922019-02-23 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo Singha, Santu K. Muhammad, Ilias Ibrahim, Mohamed Ali Wang, Mei Ashpole, Nicole M. Shariat-Madar, Zia Molecules Article Although 4-O-Methylhonokiol (MH) effects on neuronal and immune cells have been established, it is still unclear whether MH can cause a change in the structure and function of the cardiovascular system. The overarching goal of this study was to evaluate the effects of MH, isolated from Magnolia grandiflora, on the development of the heart and vasculature in a Japanese medaka model in vivo to predict human health risks. We analyzed the toxicity of MH in different life-stages of medaka embryos. MH uptake into medaka embryos was quantified. The LC(50) of two different exposure windows (stages 9–36 (0–6 days post fertilization (dpf)) and 25–36 (2–6 dpf)) were 5.3 ± 0.1 μM and 9.9 ± 0.2 μM. Survival, deformities, days to hatch, and larval locomotor response were quantified. Wnt 1 was overexpressed in MH-treated embryos indicating deregulation of the Wnt signaling pathway, which was associated with spinal and cardiac ventricle deformities. Overexpression of major proinflammatory mediators and biomarkers of the heart were detected. Our results indicated that the differential sensitivity of MH in the embryos was developmental stage-specific. Furthermore, this study demonstrated that certain molecules can serve as promising markers at the transcriptional and phenotypical levels, responding to absorption of MH in the developing embryo. MDPI 2019-01-29 /pmc/articles/PMC6384692/ /pubmed/30699965 http://dx.doi.org/10.3390/molecules24030475 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 Singha, Santu K. Muhammad, Ilias Ibrahim, Mohamed Ali Wang, Mei Ashpole, Nicole M. Shariat-Madar, Zia 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo |
title | 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo |
title_full | 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo |
title_fullStr | 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo |
title_full_unstemmed | 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo |
title_short | 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo |
title_sort | 4-o-methylhonokiol influences normal cardiovascular development in medaka embryo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384692/ https://www.ncbi.nlm.nih.gov/pubmed/30699965 http://dx.doi.org/10.3390/molecules24030475 |
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