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Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning

Chronic liver diseases affect more than 1 billion people worldwide and represent one of the main public health issues. Nonalcoholic fatty liver disease (NAFLD) accounts for the majority of mortal cases, while there is no currently approved therapeutics for its treatment. One of the prospective appro...

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Autores principales: Orlov, Alexey, Semenov, Savva, Rukhovich, Gleb, Sarycheva, Anastasia, Kovaleva, Oxana, Semenov, Alexander, Ermakova, Elena, Gubareva, Ekaterina, Bugrova, Anna E., Kononikhin, Alexey, Fedoros, Elena I., Nikolaev, Evgeny, Zherebker, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781348/
https://www.ncbi.nlm.nih.gov/pubmed/36555683
http://dx.doi.org/10.3390/ijms232416025
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author Orlov, Alexey
Semenov, Savva
Rukhovich, Gleb
Sarycheva, Anastasia
Kovaleva, Oxana
Semenov, Alexander
Ermakova, Elena
Gubareva, Ekaterina
Bugrova, Anna E.
Kononikhin, Alexey
Fedoros, Elena I.
Nikolaev, Evgeny
Zherebker, Alexander
author_facet Orlov, Alexey
Semenov, Savva
Rukhovich, Gleb
Sarycheva, Anastasia
Kovaleva, Oxana
Semenov, Alexander
Ermakova, Elena
Gubareva, Ekaterina
Bugrova, Anna E.
Kononikhin, Alexey
Fedoros, Elena I.
Nikolaev, Evgeny
Zherebker, Alexander
author_sort Orlov, Alexey
collection PubMed
description Chronic liver diseases affect more than 1 billion people worldwide and represent one of the main public health issues. Nonalcoholic fatty liver disease (NAFLD) accounts for the majority of mortal cases, while there is no currently approved therapeutics for its treatment. One of the prospective approaches to NAFLD therapy is to use a mixture of natural compounds. They showed effectiveness in alleviating NAFLD-related conditions including steatosis, fibrosis, etc. However, understanding the mechanism of action of such mixtures is important for their rational application. In this work, we propose a new dereplication workflow for deciphering the mechanism of action of the lignin-derived natural compound mixture. The workflow combines the analysis of molecular components with high-resolution mass spectrometry, selective chemical tagging and deuterium labeling, liver tissue penetration examination, assessment of biological activity in vitro, and computational chemistry tools used to generate putative structural candidates. Molecular docking was used to propose the potential mechanism of action of these structures, which was assessed by a proteomic experiment.
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spelling pubmed-97813482022-12-24 Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning Orlov, Alexey Semenov, Savva Rukhovich, Gleb Sarycheva, Anastasia Kovaleva, Oxana Semenov, Alexander Ermakova, Elena Gubareva, Ekaterina Bugrova, Anna E. Kononikhin, Alexey Fedoros, Elena I. Nikolaev, Evgeny Zherebker, Alexander Int J Mol Sci Article Chronic liver diseases affect more than 1 billion people worldwide and represent one of the main public health issues. Nonalcoholic fatty liver disease (NAFLD) accounts for the majority of mortal cases, while there is no currently approved therapeutics for its treatment. One of the prospective approaches to NAFLD therapy is to use a mixture of natural compounds. They showed effectiveness in alleviating NAFLD-related conditions including steatosis, fibrosis, etc. However, understanding the mechanism of action of such mixtures is important for their rational application. In this work, we propose a new dereplication workflow for deciphering the mechanism of action of the lignin-derived natural compound mixture. The workflow combines the analysis of molecular components with high-resolution mass spectrometry, selective chemical tagging and deuterium labeling, liver tissue penetration examination, assessment of biological activity in vitro, and computational chemistry tools used to generate putative structural candidates. Molecular docking was used to propose the potential mechanism of action of these structures, which was assessed by a proteomic experiment. MDPI 2022-12-16 /pmc/articles/PMC9781348/ /pubmed/36555683 http://dx.doi.org/10.3390/ijms232416025 Text en © 2022 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
Orlov, Alexey
Semenov, Savva
Rukhovich, Gleb
Sarycheva, Anastasia
Kovaleva, Oxana
Semenov, Alexander
Ermakova, Elena
Gubareva, Ekaterina
Bugrova, Anna E.
Kononikhin, Alexey
Fedoros, Elena I.
Nikolaev, Evgeny
Zherebker, Alexander
Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning
title Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning
title_full Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning
title_fullStr Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning
title_full_unstemmed Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning
title_short Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning
title_sort hepatoprotective activity of lignin-derived polyphenols dereplicated using high-resolution mass spectrometry, in vivo experiments, and deep learning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781348/
https://www.ncbi.nlm.nih.gov/pubmed/36555683
http://dx.doi.org/10.3390/ijms232416025
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