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A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse

Cerebral ischemia, and, as a result, insult, attacks up to 15 million people yearly in the world. In this connection, the development of effective preventive programs and methods of therapy has become one of the most urgent problems in modern angiology and pharmacology. The cytoprotective action of...

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Autores principales: Varlamova, Elena G., Uspalenko, Nina I., Khmil, Natalia V., Shigaeva, Maria I., Stepanov, Mikhail R., Ananyan, Mikhail A., Timchenko, Maria A., Molchanov, Maxim V., Mironova, Galina D., Turovsky, Egor A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380368/
https://www.ncbi.nlm.nih.gov/pubmed/37511195
http://dx.doi.org/10.3390/ijms241411436
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author Varlamova, Elena G.
Uspalenko, Nina I.
Khmil, Natalia V.
Shigaeva, Maria I.
Stepanov, Mikhail R.
Ananyan, Mikhail A.
Timchenko, Maria A.
Molchanov, Maxim V.
Mironova, Galina D.
Turovsky, Egor A.
author_facet Varlamova, Elena G.
Uspalenko, Nina I.
Khmil, Natalia V.
Shigaeva, Maria I.
Stepanov, Mikhail R.
Ananyan, Mikhail A.
Timchenko, Maria A.
Molchanov, Maxim V.
Mironova, Galina D.
Turovsky, Egor A.
author_sort Varlamova, Elena G.
collection PubMed
description Cerebral ischemia, and, as a result, insult, attacks up to 15 million people yearly in the world. In this connection, the development of effective preventive programs and methods of therapy has become one of the most urgent problems in modern angiology and pharmacology. The cytoprotective action of taxifolin (TAX) in ischemia is well known, but its limitations are also known due to its poor solubility and low capacity to pass through the hematoencephalic barrier. Molecular mechanisms underlying the protective effect of TAX in complex systems such as the brain remain poorly understood. It is known that the main cell types of the brain are neurons, astrocytes, and microglia, which regulate the activity of each other through neuroglial interactions. In this work, a comparative study of cytoprotective mechanisms of the effect of TAX and its new water-soluble form aqua taxifolin (aqTAX) was performed on cultured brain cells under ischemia-like conditions (oxygen–glucose deprivation (OGD)) followed by the reoxygenation of the culture medium. The concentration dependences of the protective effects of both taxifolin forms were determined using fluorescence microscopy, PCR analysis, and vitality tests. It was found that TAX began to effectively inhibit necrosis and the late stages of apoptosis in the concentration range of 30–100 µg/mL, with aqTAX in the range of 10–30 µg/mL. At the level of gene expression, aqTAX affected a larger number of genes than TAX; enhanced the basic and OGD/R-induced expression of genes encoding ROS-scavenging proteins with a higher efficiency, as well as anti-inflammatory and antiapoptotic proteins; and lowered the level of excitatory glutamate receptors. As a result, aqTAX significantly inhibited the OGD-induced increase in the Ca(2+) levels in the cytosol ([Ca(2+)](i)) in neurons and astrocytes under ischemic conditions. After a 40 min preincubation of cells with aqTAX under hypoxic conditions, these Ca(2+) signals were completely inhibited, resulting in an almost complete suppression of necrotic death of cerebral cortical cells, which was not observed with the use of classical TAX.
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spelling pubmed-103803682023-07-29 A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse Varlamova, Elena G. Uspalenko, Nina I. Khmil, Natalia V. Shigaeva, Maria I. Stepanov, Mikhail R. Ananyan, Mikhail A. Timchenko, Maria A. Molchanov, Maxim V. Mironova, Galina D. Turovsky, Egor A. Int J Mol Sci Article Cerebral ischemia, and, as a result, insult, attacks up to 15 million people yearly in the world. In this connection, the development of effective preventive programs and methods of therapy has become one of the most urgent problems in modern angiology and pharmacology. The cytoprotective action of taxifolin (TAX) in ischemia is well known, but its limitations are also known due to its poor solubility and low capacity to pass through the hematoencephalic barrier. Molecular mechanisms underlying the protective effect of TAX in complex systems such as the brain remain poorly understood. It is known that the main cell types of the brain are neurons, astrocytes, and microglia, which regulate the activity of each other through neuroglial interactions. In this work, a comparative study of cytoprotective mechanisms of the effect of TAX and its new water-soluble form aqua taxifolin (aqTAX) was performed on cultured brain cells under ischemia-like conditions (oxygen–glucose deprivation (OGD)) followed by the reoxygenation of the culture medium. The concentration dependences of the protective effects of both taxifolin forms were determined using fluorescence microscopy, PCR analysis, and vitality tests. It was found that TAX began to effectively inhibit necrosis and the late stages of apoptosis in the concentration range of 30–100 µg/mL, with aqTAX in the range of 10–30 µg/mL. At the level of gene expression, aqTAX affected a larger number of genes than TAX; enhanced the basic and OGD/R-induced expression of genes encoding ROS-scavenging proteins with a higher efficiency, as well as anti-inflammatory and antiapoptotic proteins; and lowered the level of excitatory glutamate receptors. As a result, aqTAX significantly inhibited the OGD-induced increase in the Ca(2+) levels in the cytosol ([Ca(2+)](i)) in neurons and astrocytes under ischemic conditions. After a 40 min preincubation of cells with aqTAX under hypoxic conditions, these Ca(2+) signals were completely inhibited, resulting in an almost complete suppression of necrotic death of cerebral cortical cells, which was not observed with the use of classical TAX. MDPI 2023-07-14 /pmc/articles/PMC10380368/ /pubmed/37511195 http://dx.doi.org/10.3390/ijms241411436 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
Varlamova, Elena G.
Uspalenko, Nina I.
Khmil, Natalia V.
Shigaeva, Maria I.
Stepanov, Mikhail R.
Ananyan, Mikhail A.
Timchenko, Maria A.
Molchanov, Maxim V.
Mironova, Galina D.
Turovsky, Egor A.
A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse
title A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse
title_full A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse
title_fullStr A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse
title_full_unstemmed A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse
title_short A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse
title_sort comparative analysis of neuroprotective properties of taxifolin and its water-soluble form in ischemia of cerebral cortical cells of the mouse
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380368/
https://www.ncbi.nlm.nih.gov/pubmed/37511195
http://dx.doi.org/10.3390/ijms241411436
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