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Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD)
9′-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mod...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049354/ https://www.ncbi.nlm.nih.gov/pubmed/36982372 http://dx.doi.org/10.3390/ijms24065296 |
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author | Fontaine, Valérie Balducci, Christine Dinan, Laurence Monteiro, Elodie Boumedine, Thinhinane Fournié, Mylène Nguyen, Vincent Guibout, Louis Clatot, Justine Latil, Mathilde Veillet, Stanislas Sahel, José-Alain Lafont, René Dilda, Pierre J. Camelo, Serge |
author_facet | Fontaine, Valérie Balducci, Christine Dinan, Laurence Monteiro, Elodie Boumedine, Thinhinane Fournié, Mylène Nguyen, Vincent Guibout, Louis Clatot, Justine Latil, Mathilde Veillet, Stanislas Sahel, José-Alain Lafont, René Dilda, Pierre J. Camelo, Serge |
author_sort | Fontaine, Valérie |
collection | PubMed |
description | 9′-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of BIO203, a novel norbixin amide conjugate. Compared to norbixin, BIO203 displays improved stability at all temperatures tested for up to 18 months. In vitro, BIO203 and norbixin share a similar mode of action involving the inhibition of PPARs, NF-κB, and AP-1 transactivations. The two compounds also reduce IL-6, IL-8, and VEGF expression induced by A2E. In vivo, ocular maximal concentration and BIO203 plasma exposure are increased compared to those of norbixin. Moreover, BIO203 administered systemically protects visual functions and retinal structure in albino rats subjected to blue-light illumination and in the retinal degeneration model of Abca4(−/−) Rdh8(−/−) double knock-out mice following 6 months of oral complementation. In conclusion, we report here that BIO203 and norbixin share similar modes of action and protective effects in vitro and in vivo. BIO203, with its improved pharmacokinetic and stability properties, could be developed for the treatment of retinal degenerative diseases such as AMD. |
format | Online Article Text |
id | pubmed-10049354 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100493542023-03-29 Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD) Fontaine, Valérie Balducci, Christine Dinan, Laurence Monteiro, Elodie Boumedine, Thinhinane Fournié, Mylène Nguyen, Vincent Guibout, Louis Clatot, Justine Latil, Mathilde Veillet, Stanislas Sahel, José-Alain Lafont, René Dilda, Pierre J. Camelo, Serge Int J Mol Sci Article 9′-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of BIO203, a novel norbixin amide conjugate. Compared to norbixin, BIO203 displays improved stability at all temperatures tested for up to 18 months. In vitro, BIO203 and norbixin share a similar mode of action involving the inhibition of PPARs, NF-κB, and AP-1 transactivations. The two compounds also reduce IL-6, IL-8, and VEGF expression induced by A2E. In vivo, ocular maximal concentration and BIO203 plasma exposure are increased compared to those of norbixin. Moreover, BIO203 administered systemically protects visual functions and retinal structure in albino rats subjected to blue-light illumination and in the retinal degeneration model of Abca4(−/−) Rdh8(−/−) double knock-out mice following 6 months of oral complementation. In conclusion, we report here that BIO203 and norbixin share similar modes of action and protective effects in vitro and in vivo. BIO203, with its improved pharmacokinetic and stability properties, could be developed for the treatment of retinal degenerative diseases such as AMD. MDPI 2023-03-10 /pmc/articles/PMC10049354/ /pubmed/36982372 http://dx.doi.org/10.3390/ijms24065296 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fontaine, Valérie Balducci, Christine Dinan, Laurence Monteiro, Elodie Boumedine, Thinhinane Fournié, Mylène Nguyen, Vincent Guibout, Louis Clatot, Justine Latil, Mathilde Veillet, Stanislas Sahel, José-Alain Lafont, René Dilda, Pierre J. Camelo, Serge Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD) |
title | Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD) |
title_full | Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD) |
title_fullStr | Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD) |
title_full_unstemmed | Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD) |
title_short | Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD) |
title_sort | anti-inflammatory effects and photo- and neuro-protective properties of bio203, a new amide conjugate of norbixin, in development for the treatment of age-related macular degeneration (amd) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049354/ https://www.ncbi.nlm.nih.gov/pubmed/36982372 http://dx.doi.org/10.3390/ijms24065296 |
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