Oridonin Inhibits Inflammation of Epithelial Cells Dual-targeting of CD31 Keap1 to Ameliorate Acute Lung Injury

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Apr 24

PMID 37090710

Authors

Yue Zhao

Hua Jin

Kawai Lei

Li-Ping Bai

Hudan Pan

Caiyan Wang

Xiaoming Zhu

Yanqing Tang

Zhengyang Guo

Jiye Cai

Ting Li

Affiliations

Soon will be listed here.

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.

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