Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway

Acute lung injury (ALI) is a severe clinical disorder characterized by dysregulated inflammatory responses, leading to high rates of morbidity and mortality. Cinobufagin, a primary component isolated from cinobufotalin, exerts strong anticancer effects. However, there are few reports on its role in...

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Main Authors: Cheng Wang, Xianghuang Mei, Yanrong Wu, Yuting Yang, Zhenguo Zeng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.994625/full
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author Cheng Wang
Cheng Wang
Xianghuang Mei
Yanrong Wu
Yuting Yang
Zhenguo Zeng
author_facet Cheng Wang
Cheng Wang
Xianghuang Mei
Yanrong Wu
Yuting Yang
Zhenguo Zeng
author_sort Cheng Wang
collection DOAJ
description Acute lung injury (ALI) is a severe clinical disorder characterized by dysregulated inflammatory responses, leading to high rates of morbidity and mortality. Cinobufagin, a primary component isolated from cinobufotalin, exerts strong anticancer effects. However, there are few reports on its role in ALI, and it is unclear whether cinobufagin affects lipopolysaccharide (LPS)-induced ALI. Therefore, the present study aimed to investigate the effect of cinobufagin on LPS-induced ALI and to assess its potential mechanism of action. The results showed that cinobufagin alleviated lung histopathological changes and protected the permeability of lung tissues in LPS-induced ALI. In addition, cinobufagin effectively suppressed inflammatory responses through the induction of autophagy in LPS-induced ALI cells and in a mouse model. Moreover, cinobufagin enhanced autophagy through the p53/mTOR pathway in LPS-induced ALI. Herein, it was reported for the first time that cinobufagin inhibited the inflammatory response of LPS-induced ALI, which laid the foundation for further understanding and development of cinobufagin as a potential new drug for ALI.
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spelling doaj.art-d1898006b04f4d7cbc60d3ea67d0be352022-12-22T02:55:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.994625994625Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathwayCheng Wang0Cheng Wang1Xianghuang Mei2Yanrong Wu3Yuting Yang4Zhenguo Zeng5Department of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Respiratory Disease, Nanchang, ChinaDepartment of Gastrointestinal Surgery, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, ChinaDepartment of Ophthalmology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaDepartment of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaAcute lung injury (ALI) is a severe clinical disorder characterized by dysregulated inflammatory responses, leading to high rates of morbidity and mortality. Cinobufagin, a primary component isolated from cinobufotalin, exerts strong anticancer effects. However, there are few reports on its role in ALI, and it is unclear whether cinobufagin affects lipopolysaccharide (LPS)-induced ALI. Therefore, the present study aimed to investigate the effect of cinobufagin on LPS-induced ALI and to assess its potential mechanism of action. The results showed that cinobufagin alleviated lung histopathological changes and protected the permeability of lung tissues in LPS-induced ALI. In addition, cinobufagin effectively suppressed inflammatory responses through the induction of autophagy in LPS-induced ALI cells and in a mouse model. Moreover, cinobufagin enhanced autophagy through the p53/mTOR pathway in LPS-induced ALI. Herein, it was reported for the first time that cinobufagin inhibited the inflammatory response of LPS-induced ALI, which laid the foundation for further understanding and development of cinobufagin as a potential new drug for ALI.https://www.frontiersin.org/articles/10.3389/fphar.2022.994625/fullacute lung injurycinobufaginlipopolysaccharideautophagyp53mTOR
spellingShingle Cheng Wang
Cheng Wang
Xianghuang Mei
Yanrong Wu
Yuting Yang
Zhenguo Zeng
Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway
Frontiers in Pharmacology
acute lung injury
cinobufagin
lipopolysaccharide
autophagy
p53
mTOR
title Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway
title_full Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway
title_fullStr Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway
title_full_unstemmed Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway
title_short Cinobufagin alleviates lipopolysaccharide-induced acute lung injury by regulating autophagy through activation of the p53/mTOR pathway
title_sort cinobufagin alleviates lipopolysaccharide induced acute lung injury by regulating autophagy through activation of the p53 mtor pathway
topic acute lung injury
cinobufagin
lipopolysaccharide
autophagy
p53
mTOR
url https://www.frontiersin.org/articles/10.3389/fphar.2022.994625/full
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AT xianghuangmei cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway
AT yanrongwu cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway
AT yutingyang cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway
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