Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway

Acute lung injury (ALI) is a major pathological problem characterized by severe inflammatory reactions and is a critical disease with high clinical morbidity and mortality. Liensinine, a major isoquinoline alkaloid, is extracted from the green embryos of mature Nelumbonaceae seeds. It has been repor...

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Main Authors: Cheng Wang, Kang Zou, Yunlian Diao, Chaoqi Zhou, Jia Zhou, Yuting Yang, Zhenguo Zeng
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332223016116
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author Cheng Wang
Kang Zou
Yunlian Diao
Chaoqi Zhou
Jia Zhou
Yuting Yang
Zhenguo Zeng
author_facet Cheng Wang
Kang Zou
Yunlian Diao
Chaoqi Zhou
Jia Zhou
Yuting Yang
Zhenguo Zeng
author_sort Cheng Wang
collection DOAJ
description Acute lung injury (ALI) is a major pathological problem characterized by severe inflammatory reactions and is a critical disease with high clinical morbidity and mortality. Liensinine, a major isoquinoline alkaloid, is extracted from the green embryos of mature Nelumbonaceae seeds. It has been reported to have an inhibitory effect on tumors. However, the effects of liensinine on ALI have not been reported to-date. The aim of this study was to explore the inhibitory effects of liensinine on lipopolysaccharide (LPS)-induced ALI and its possible mechanism. We found that liensinine significantly reduced LPS-induced ALI and reduced the production of inflammatory factors IL-6, IL-8, and TNF-α. In addition, liensinine blocked autophagic flux and increased the number of autophagosomes by upregulating LC3-II/I and p62 protein levels. More importantly, pretreatment with the early stages autophagy inhibitor 3-Methyladenine (3-MA) can reverse the inhibitory effects of liensinine on the secretion of inflammatory factors in ALI. The PI3K/AKT/mTOR pathway is involved in LPS-induced autophagy regulated by liensinine in ALI. In summary, this study suggests that liensinine inhibits the production of inflammatory factors in LPS-induced ALI by regulating autophagy via the PI3K/AKT/mTOR pathway, which may provide a new therapeutic strategy to alleviate ALI.
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spelling doaj.art-9ac139ebdc9b4e0e9c9815594f9e110f2023-11-12T04:39:24ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115813Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathwayCheng Wang0Kang Zou1Yunlian Diao2Chaoqi Zhou3Jia Zhou4Yuting Yang5Zhenguo Zeng6Department of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China; Jiangxi Institute of Respiratory Disease, Nanchang 330052, ChinaDepartment of Critical Care Medicine, the First Affiliated Hospital of Gannan Medical College, Gannan Medical College, Ganzhou 341000, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China; Jiangxi Institute of Respiratory Disease, Nanchang 330052, ChinaDepartment of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China; Jiangxi Institute of Respiratory Disease, Nanchang 330052, ChinaDepartment of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Critical Care Medicine, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China; Corresponding author.Acute lung injury (ALI) is a major pathological problem characterized by severe inflammatory reactions and is a critical disease with high clinical morbidity and mortality. Liensinine, a major isoquinoline alkaloid, is extracted from the green embryos of mature Nelumbonaceae seeds. It has been reported to have an inhibitory effect on tumors. However, the effects of liensinine on ALI have not been reported to-date. The aim of this study was to explore the inhibitory effects of liensinine on lipopolysaccharide (LPS)-induced ALI and its possible mechanism. We found that liensinine significantly reduced LPS-induced ALI and reduced the production of inflammatory factors IL-6, IL-8, and TNF-α. In addition, liensinine blocked autophagic flux and increased the number of autophagosomes by upregulating LC3-II/I and p62 protein levels. More importantly, pretreatment with the early stages autophagy inhibitor 3-Methyladenine (3-MA) can reverse the inhibitory effects of liensinine on the secretion of inflammatory factors in ALI. The PI3K/AKT/mTOR pathway is involved in LPS-induced autophagy regulated by liensinine in ALI. In summary, this study suggests that liensinine inhibits the production of inflammatory factors in LPS-induced ALI by regulating autophagy via the PI3K/AKT/mTOR pathway, which may provide a new therapeutic strategy to alleviate ALI.http://www.sciencedirect.com/science/article/pii/S0753332223016116Acute lung injuryAutophagic fluxLiensininePI3K/AKT/mTOR pathway
spellingShingle Cheng Wang
Kang Zou
Yunlian Diao
Chaoqi Zhou
Jia Zhou
Yuting Yang
Zhenguo Zeng
Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway
Biomedicine & Pharmacotherapy
Acute lung injury
Autophagic flux
Liensinine
PI3K/AKT/mTOR pathway
title Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway
title_full Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway
title_fullStr Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway
title_full_unstemmed Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway
title_short Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway
title_sort liensinine alleviates lps induced acute lung injury by blocking autophagic flux via pi3k akt mtor signaling pathway
topic Acute lung injury
Autophagic flux
Liensinine
PI3K/AKT/mTOR pathway
url http://www.sciencedirect.com/science/article/pii/S0753332223016116
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