PMID- 35340214
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220405
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - The Activation of AMPK/NRF2 Pathway in Lung Epithelial Cells Is Involved in the 
      Protective Effects of Kinsenoside on Lipopolysaccharide-Induced Acute Lung 
      Injury.
PG  - 3589277
LID - 10.1155/2022/3589277 [doi]
LID - 3589277
AB  - The disorder of mitochondrial dynamic equilibrium of lung epithelial cell is one 
      of the critical causes of acute lung injury (ALI). Kinsenoside (Kin) serves as an 
      active small-molecule component derived from traditional medicinal herb 
      displaying multiple pharmacological actions in cancers, hyperglycemia, and liver 
      disease. The objective of this study was to investigate the effects of Kin on 
      lipopolysaccharide- (LPS-) induced ALI and further explore possible molecular 
      mechanisms. Kin was administered orally (100 mg/kg/day) for 7 consecutive days 
      before LPS instillation (5 mg/kg). After 12 hours, pathological injury, 
      inflammatory response, and oxidative stress were detected. The results 
      demonstrated that Kin significantly alleviated lung pathological injury and 
      decreased the infiltration of inflammatory cells and the release of inflammatory 
      mediators in bronchoalveolar lavage fluid (BALF), apart from inhibiting the 
      production of reactive oxygen species (ROS) and lipid peroxidation. Meanwhile, 
      Kin also promoted mitochondrial fusion and restrained mitochondrial fission in 
      mice with ALI. In terms of mechanism, Kin pretreatment increased the 
      phosphorylation of AMP-activated protein kinase (AMPK) and the protein level of 
      nuclear factor erythroid 2-related factor 2 (NRF2). In Ampk-alpha knockout mice 
      challenged with LPS, Kin lost its pulmonary protective effects, accompanied by 
      lower NRF2 level. In vitro experiments further unveiled that either AMPK 
      inhibition by Compound C or NRF2 knockdown by siRNA abolished the protective 
      roles of Kin in LPS-treated A549 lung epithelial cells. And NRF2 activator TAT-14 
      could reverse the effects of Ampk-alpha deficiency. In conclusion, Kin possesses the 
      ability to prevent LPS-induced ALI by modulating mitochondrial dynamic 
      equilibrium in lung epithelial cell in an AMPK/NRF2-dependent manner.
CI  - Copyright (c) 2022 Yue Yang et al.
FAU - Yang, Yue
AU  - Yang Y
AD  - Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, 
      China.
FAU - Zhong, Zhen-Tong
AU  - Zhong ZT
AD  - Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 
      430060, China.
FAU - Xiao, Yong-Guang
AU  - Xiao YG
AUID- ORCID: 0000-0003-1769-7687
AD  - Department of Thoracic, Renmin Hospital of Wuhan University, Wuhan 430060, China.
FAU - Chen, Hong-Bin
AU  - Chen HB
AUID- ORCID: 0000-0001-8021-8568
AD  - Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan 
      University, Wuhan 430060, China.
LA  - eng
PT  - Journal Article
DEP - 20220318
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (3-glucopyranosyloxybutanolide)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Monosaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - OL659KIY4X (4-Butyrolactone)
SB  - IM
MH  - 4-Butyrolactone/analogs & derivatives
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Acute Lung Injury/chemically induced/drug therapy/metabolism
MH  - Animals
MH  - Epithelial Cells/metabolism
MH  - *Lipopolysaccharides/pharmacology
MH  - Lung/pathology
MH  - Mice
MH  - Monosaccharides
MH  - NF-E2-Related Factor 2/metabolism
PMC - PMC8956386
COIS- The authors declare no conflicts of interest.
EDAT- 2022/03/29 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/03/18
CRDT- 2022/03/28 05:05
PHST- 2021/09/29 00:00 [received]
PHST- 2022/01/06 00:00 [revised]
PHST- 2022/01/28 00:00 [accepted]
PHST- 2022/03/28 05:05 [entrez]
PHST- 2022/03/29 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2022/03/18 00:00 [pmc-release]
AID - 10.1155/2022/3589277 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Mar 18;2022:3589277. doi: 10.1155/2022/3589277. 
      eCollection 2022.