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


ABSTRACT:

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.

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC10116055 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Oridonin inhibits inflammation of epithelial cells <i>via</i> dual-targeting of CD31 Keap1 to ameliorate acute lung injury.

Zhao Yue Y   Jin Hua H   Lei Kawai K   Bai Li-Ping LP   Pan Hudan H   Wang Caiyan C   Zhu Xiaoming X   Tang Yanqing Y   Guo Zhengyang Z   Cai Jiye J   Li Ting T  

Frontiers in immunology 20230406


<h4>Introdcution</h4>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.<h4>Methods</h4>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 c  ...[more]

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