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...
Main Authors: | , , , , |
---|---|
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 |
_version_ | 1811303587667509248 |
---|---|
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. |
first_indexed | 2024-04-13T07:50:42Z |
format | Article |
id | doaj.art-d1898006b04f4d7cbc60d3ea67d0be35 |
institution | Directory Open Access Journal |
issn | 1663-9812 |
language | English |
last_indexed | 2024-04-13T07:50:42Z |
publishDate | 2022-11-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Pharmacology |
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 |
work_keys_str_mv | AT chengwang cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway AT chengwang cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway AT xianghuangmei cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway AT yanrongwu cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway AT yutingyang cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway AT zhenguozeng cinobufaginalleviateslipopolysaccharideinducedacutelunginjurybyregulatingautophagythroughactivationofthep53mtorpathway |