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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...

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Autores principales: Qi, Feiran, Liu, Yan, Zhang, Kunlin, Zhang, Yanzhenzi, Xu, Ke, Zhou, Mei, Zhao, Huinan, Zhu, Shuolin, Chen, Jianxin, Li, Ping, Du, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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