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Systems biology reveals anatabine to be an NRF2 activator

Anatabine, an alkaloid present in plants of the So lanaceae family (including tobacco and eggplant), has been shown to ameliorate chronic inflammatory conditions in mouse models, such as Alzheimer’s disease, Hashimoto’s thyroiditis, multiple sclerosis, and intestinal inflammation. However, the mecha...

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Autores principales: Messinis, Dimitris E., Poussin, Carine, Latino, Diogo A. R. S., Eb-Levadoux, Yvan, Dulize, Remi, Peric, Dariusz, Guedj, Emmanuel, Titz, Bjoern, Ivanov, Nikolai V., Peitsch, Manuel C., Hoeng, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708905/
https://www.ncbi.nlm.nih.gov/pubmed/36467029
http://dx.doi.org/10.3389/fphar.2022.1011184
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author Messinis, Dimitris E.
Poussin, Carine
Latino, Diogo A. R. S.
Eb-Levadoux, Yvan
Dulize, Remi
Peric, Dariusz
Guedj, Emmanuel
Titz, Bjoern
Ivanov, Nikolai V.
Peitsch, Manuel C.
Hoeng, Julia
author_facet Messinis, Dimitris E.
Poussin, Carine
Latino, Diogo A. R. S.
Eb-Levadoux, Yvan
Dulize, Remi
Peric, Dariusz
Guedj, Emmanuel
Titz, Bjoern
Ivanov, Nikolai V.
Peitsch, Manuel C.
Hoeng, Julia
author_sort Messinis, Dimitris E.
collection PubMed
description Anatabine, an alkaloid present in plants of the So lanaceae family (including tobacco and eggplant), has been shown to ameliorate chronic inflammatory conditions in mouse models, such as Alzheimer’s disease, Hashimoto’s thyroiditis, multiple sclerosis, and intestinal inflammation. However, the mechanisms of action of anatabine remain unclear. To understand the impact of anatabine on cellular systems and identify the molecular pathways that are perturbed, we designed a study to examine the concentration-dependent effects of anatabine on various cell types by using a systems pharmacology approach. The resulting dataset, consisting of measurements of various omics data types at different time points, was analyzed by using multiple computational techniques. To identify concentration-dependent activated pathways, we performed linear modeling followed by gene set enrichment. To predict the functional partners of anatabine and the involved pathways, we harnessed the LINCS L1000 dataset’s wealth of information and implemented integer linear programming on directed graphs, respectively. Finally, we experimentally verified our key computational predictions. Using an appropriate luciferase reporter cell system, we were able to demonstrate that anatabine treatment results in NRF2 (nuclear factor-erythroid factor 2-related factor 2) translocation, and our systematic phosphoproteomic assays showed that anatabine treatment results in activation of MAPK signaling. While there are certain areas to be explored in deciphering the exact anti-inflammatory mechanisms of action of anatabine and other NRF2 activators, we believe that anatabine constitutes an interesting molecule for its therapeutic potential in NRF2-related diseases.
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spelling pubmed-97089052022-12-01 Systems biology reveals anatabine to be an NRF2 activator Messinis, Dimitris E. Poussin, Carine Latino, Diogo A. R. S. Eb-Levadoux, Yvan Dulize, Remi Peric, Dariusz Guedj, Emmanuel Titz, Bjoern Ivanov, Nikolai V. Peitsch, Manuel C. Hoeng, Julia Front Pharmacol Pharmacology Anatabine, an alkaloid present in plants of the So lanaceae family (including tobacco and eggplant), has been shown to ameliorate chronic inflammatory conditions in mouse models, such as Alzheimer’s disease, Hashimoto’s thyroiditis, multiple sclerosis, and intestinal inflammation. However, the mechanisms of action of anatabine remain unclear. To understand the impact of anatabine on cellular systems and identify the molecular pathways that are perturbed, we designed a study to examine the concentration-dependent effects of anatabine on various cell types by using a systems pharmacology approach. The resulting dataset, consisting of measurements of various omics data types at different time points, was analyzed by using multiple computational techniques. To identify concentration-dependent activated pathways, we performed linear modeling followed by gene set enrichment. To predict the functional partners of anatabine and the involved pathways, we harnessed the LINCS L1000 dataset’s wealth of information and implemented integer linear programming on directed graphs, respectively. Finally, we experimentally verified our key computational predictions. Using an appropriate luciferase reporter cell system, we were able to demonstrate that anatabine treatment results in NRF2 (nuclear factor-erythroid factor 2-related factor 2) translocation, and our systematic phosphoproteomic assays showed that anatabine treatment results in activation of MAPK signaling. While there are certain areas to be explored in deciphering the exact anti-inflammatory mechanisms of action of anatabine and other NRF2 activators, we believe that anatabine constitutes an interesting molecule for its therapeutic potential in NRF2-related diseases. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9708905/ /pubmed/36467029 http://dx.doi.org/10.3389/fphar.2022.1011184 Text en Copyright © 2022 Messinis, Poussin, Latino, Eb-Levadoux, Dulize, Peric, Guedj, Titz, Ivanov, Peitsch and Hoeng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Messinis, Dimitris E.
Poussin, Carine
Latino, Diogo A. R. S.
Eb-Levadoux, Yvan
Dulize, Remi
Peric, Dariusz
Guedj, Emmanuel
Titz, Bjoern
Ivanov, Nikolai V.
Peitsch, Manuel C.
Hoeng, Julia
Systems biology reveals anatabine to be an NRF2 activator
title Systems biology reveals anatabine to be an NRF2 activator
title_full Systems biology reveals anatabine to be an NRF2 activator
title_fullStr Systems biology reveals anatabine to be an NRF2 activator
title_full_unstemmed Systems biology reveals anatabine to be an NRF2 activator
title_short Systems biology reveals anatabine to be an NRF2 activator
title_sort systems biology reveals anatabine to be an nrf2 activator
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708905/
https://www.ncbi.nlm.nih.gov/pubmed/36467029
http://dx.doi.org/10.3389/fphar.2022.1011184
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