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Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury

INTRODCUTION: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is the...

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Autores principales: Zhao, Yue, Jin, Hua, Lei, Kawai, Bai, Li-Ping, Pan, Hudan, Wang, Caiyan, Zhu, Xiaoming, Tang, Yanqing, Guo, Zhengyang, Cai, Jiye, Li, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116055/
https://www.ncbi.nlm.nih.gov/pubmed/37090710
http://dx.doi.org/10.3389/fimmu.2023.1163397
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author Zhao, Yue
Jin, Hua
Lei, Kawai
Bai, Li-Ping
Pan, Hudan
Wang, Caiyan
Zhu, Xiaoming
Tang, Yanqing
Guo, Zhengyang
Cai, Jiye
Li, Ting
author_facet Zhao, Yue
Jin, Hua
Lei, Kawai
Bai, Li-Ping
Pan, Hudan
Wang, Caiyan
Zhu, Xiaoming
Tang, Yanqing
Guo, Zhengyang
Cai, Jiye
Li, Ting
author_sort Zhao, Yue
collection PubMed
description INTRODCUTION: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary. METHODS: We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells. RESULTS: Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells. DISCUSSION: Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.
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spelling pubmed-101160552023-04-21 Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury Zhao, Yue Jin, Hua Lei, Kawai Bai, Li-Ping Pan, Hudan Wang, Caiyan Zhu, Xiaoming Tang, Yanqing Guo, Zhengyang Cai, Jiye Li, Ting Front Immunol Immunology INTRODCUTION: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary. METHODS: We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells. RESULTS: Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells. DISCUSSION: Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy. Frontiers Media S.A. 2023-04-06 /pmc/articles/PMC10116055/ /pubmed/37090710 http://dx.doi.org/10.3389/fimmu.2023.1163397 Text en Copyright © 2023 Zhao, Jin, Lei, Bai, Pan, Wang, Zhu, Tang, Guo, Cai and Li 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 Immunology
Zhao, Yue
Jin, Hua
Lei, Kawai
Bai, Li-Ping
Pan, Hudan
Wang, Caiyan
Zhu, Xiaoming
Tang, Yanqing
Guo, Zhengyang
Cai, Jiye
Li, Ting
Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury
title Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury
title_full Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury
title_fullStr Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury
title_full_unstemmed Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury
title_short Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury
title_sort oridonin inhibits inflammation of epithelial cells via dual-targeting of cd31 keap1 to ameliorate acute lung injury
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116055/
https://www.ncbi.nlm.nih.gov/pubmed/37090710
http://dx.doi.org/10.3389/fimmu.2023.1163397
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