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Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection
Thoracic aortic aneurysm and dissection (TAAD) is a lethal cardiovascular condition without effective pharmaceutical therapy. Identifying novel drugs that target the key pathogenetic components is an urgent need. Bioinformatics analysis of pathological studies indicated “extracellular matrix organiz...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019136/ https://www.ncbi.nlm.nih.gov/pubmed/35463768 http://dx.doi.org/10.3389/fcvm.2022.871486 |
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author | Qi, Feiran Liu, Yan Zhang, Kunlin Zhang, Yanzhenzi Xu, Ke Zhou, Mei Zhao, Huinan Zhu, Shuolin Chen, Jianxin Li, Ping Du, Jie |
author_facet | Qi, Feiran Liu, Yan Zhang, Kunlin Zhang, Yanzhenzi Xu, Ke Zhou, Mei Zhao, Huinan Zhu, Shuolin Chen, Jianxin Li, Ping Du, Jie |
author_sort | Qi, Feiran |
collection | PubMed |
description | Thoracic aortic aneurysm and dissection (TAAD) is a lethal cardiovascular condition without effective pharmaceutical therapy. Identifying novel drugs that target the key pathogenetic components is an urgent need. Bioinformatics analysis of pathological studies indicated “extracellular matrix organization” as the most significant functional pathway related to TAAD, in which matrix metallopeptidase (MMP) 2 and MMP9 ranked above other proteases. MMP1-14 were designated as the prototype molecules for docking against PubChem Compound Database using Surflex-Dock, and nine natural compounds were identified. Using a generic MMP activity assay and an aminopropionitrile (BAPN)-induced TAAD mouse model, we identified crocin as an effective MMP inhibitor, suppressing the occurrence and rupture of TAAD. Biolayer interferometry and AI/bioinformatics analyses indicated that crocin may inhibit MMP2 activity by direct binding. Possible binding sites were investigated. Overall, the integration of artificial intelligence and functional experiments identified crocin as an MMP inhibitor with strong therapeutic potential. |
format | Online Article Text |
id | pubmed-9019136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90191362022-04-21 Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection Qi, Feiran Liu, Yan Zhang, Kunlin Zhang, Yanzhenzi Xu, Ke Zhou, Mei Zhao, Huinan Zhu, Shuolin Chen, Jianxin Li, Ping Du, Jie Front Cardiovasc Med Cardiovascular Medicine Thoracic aortic aneurysm and dissection (TAAD) is a lethal cardiovascular condition without effective pharmaceutical therapy. Identifying novel drugs that target the key pathogenetic components is an urgent need. Bioinformatics analysis of pathological studies indicated “extracellular matrix organization” as the most significant functional pathway related to TAAD, in which matrix metallopeptidase (MMP) 2 and MMP9 ranked above other proteases. MMP1-14 were designated as the prototype molecules for docking against PubChem Compound Database using Surflex-Dock, and nine natural compounds were identified. Using a generic MMP activity assay and an aminopropionitrile (BAPN)-induced TAAD mouse model, we identified crocin as an effective MMP inhibitor, suppressing the occurrence and rupture of TAAD. Biolayer interferometry and AI/bioinformatics analyses indicated that crocin may inhibit MMP2 activity by direct binding. Possible binding sites were investigated. Overall, the integration of artificial intelligence and functional experiments identified crocin as an MMP inhibitor with strong therapeutic potential. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9019136/ /pubmed/35463768 http://dx.doi.org/10.3389/fcvm.2022.871486 Text en Copyright © 2022 Qi, Liu, Zhang, Zhang, Xu, Zhou, Zhao, Zhu, Chen, Li and Du. 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 | Cardiovascular Medicine Qi, Feiran Liu, Yan Zhang, Kunlin Zhang, Yanzhenzi Xu, Ke Zhou, Mei Zhao, Huinan Zhu, Shuolin Chen, Jianxin Li, Ping Du, Jie Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection |
title | Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection |
title_full | Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection |
title_fullStr | Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection |
title_full_unstemmed | Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection |
title_short | Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection |
title_sort | artificial intelligence uncovers natural mmp inhibitor crocin as a potential treatment of thoracic aortic aneurysm and dissection |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019136/ https://www.ncbi.nlm.nih.gov/pubmed/35463768 http://dx.doi.org/10.3389/fcvm.2022.871486 |
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