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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/16025 |
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| author | Alexey Orlov Savva Semenov Gleb Rukhovich Anastasia Sarycheva Oxana Kovaleva Alexander Semenov Elena Ermakova Ekaterina Gubareva Anna E. Bugrova Alexey Kononikhin Elena I. Fedoros Evgeny Nikolaev Alexander Zherebker |
| author_facet | Alexey Orlov Savva Semenov Gleb Rukhovich Anastasia Sarycheva Oxana Kovaleva Alexander Semenov Elena Ermakova Ekaterina Gubareva Anna E. Bugrova Alexey Kononikhin Elena I. Fedoros Evgeny Nikolaev Alexander Zherebker |
| author_sort | Alexey Orlov |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T16:19:06Z |
| format | Article |
| id | doaj.art-c1c85f44bd6d4d59a0192d5445994ada |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:06Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c1c85f44bd6d4d59a0192d5445994ada2023-11-24T15:31:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241602510.3390/ijms232416025Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep LearningAlexey Orlov0Savva Semenov1Gleb Rukhovich2Anastasia Sarycheva3Oxana Kovaleva4Alexander Semenov5Elena Ermakova6Ekaterina Gubareva7Anna E. Bugrova8Alexey Kononikhin9Elena I. Fedoros10Evgeny Nikolaev11Alexander Zherebker12Skolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaN.N. Petrov National Medical Research Center of Oncology, 68 Leningradskaya Str., 197758 Saint Petersburg, RussiaN.N. Petrov National Medical Research Center of Oncology, 68 Leningradskaya Str., 197758 Saint Petersburg, RussiaN.N. Petrov National Medical Research Center of Oncology, 68 Leningradskaya Str., 197758 Saint Petersburg, RussiaEmanuel Institute for Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, RussiaSkolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaN.N. Petrov National Medical Research Center of Oncology, 68 Leningradskaya Str., 197758 Saint Petersburg, RussiaSkolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaSkolkovo Institute of Science and Technology, 30 Bolshoy Boulevard bld. 1, 121205 Moscow, RussiaChronic 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.https://www.mdpi.com/1422-0067/23/24/16025NAFLDhepatoprotective activitycomplex mixturespolyphenolic compositiondereplicationlabeling |
| spellingShingle | Alexey Orlov Savva Semenov Gleb Rukhovich Anastasia Sarycheva Oxana Kovaleva Alexander Semenov Elena Ermakova Ekaterina Gubareva Anna E. Bugrova Alexey Kononikhin Elena I. Fedoros Evgeny Nikolaev Alexander Zherebker Hepatoprotective Activity of Lignin-Derived Polyphenols Dereplicated Using High-Resolution Mass Spectrometry, In Vivo Experiments, and Deep Learning International Journal of Molecular Sciences NAFLD hepatoprotective activity complex mixtures polyphenolic composition dereplication labeling |
| 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 | NAFLD hepatoprotective activity complex mixtures polyphenolic composition dereplication labeling |
| url | https://www.mdpi.com/1422-0067/23/24/16025 |
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