PMID- 37481848
OWN - NLM
STAT- MEDLINE
DCOM- 20230825
LR  - 20230825
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 122
DP  - 2023 Sep
TI  - Limonin, a novel AMPK activator, protects against LPS-induced acute lung injury.
PG  - 110678
LID - S1567-5769(23)01003-2 [pii]
LID - 10.1016/j.intimp.2023.110678 [doi]
AB  - AMP-activated protein kinase (AMPK) activation plays crucial roles in the 
      treatment of many oxidative stress- and inflammation-induced diseases, including 
      acute lung injury (ALI). Limonin is a naturally occurring tetracyclic 
      triterpenoid extracted from the plants of Rutaceae and Meliaceae. Limonin also 
      serves as an AMPK activator with anti-inflammatory and anti-oxidation effects. 
      However, the potential beneficial effects of limonin on ALI and the possible 
      mechanisms have never been disclosed till now. Here, the effects of limonin on 
      lipopolysaccharide (LPS)-induced ALI in C57 BL/6 mice, plus bone marrow-derived 
      macrophages (BMDM) stimulated with LPS to induce in vitro ALI model were 
      investigated. Limonin significantly improved pulmonary function and alleviated 
      lung pathological injury in LPS-induced mice. Meanwhile, limonin also markedly 
      decreased inflammation and oxidative stress in lung tissues from LPS-treated 
      mice. In vitro experiments also unveiled that limonin could decrease inflammation 
      and oxidative stress in LPS-induced BMDM in a concentration-dependent manner. 
      Mechanically, limonin could promote the activation of AMPKalpha and upregulate the 
      expression of nuclear factor erythroid 2-related factor 2 (NRF2) in lung tissues 
      and BMDM. Pharmacological inhibition of AMPKalpha by Compound C or AMPKalpha knockout 
      could abolish the pulmonary protection from limonin during ALI. In conclusion, 
      limonin mediates the activation of AMPKalpha/NRF2 pathway, providing an attractive 
      therapeutic target for ALI in the future.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Liang, Hui
AU  - Liang H
AD  - Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Liu, Gaoli
AU  - Liu G
AD  - Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Fan, Qinglu
AU  - Fan Q
AD  - Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Nie, Zhihao
AU  - Nie Z
AD  - Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Xie, Songping
AU  - Xie S
AD  - Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Zhang, Renquan
AU  - Zhang R
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, China. Electronic address: zhangrenquan@live.cn.
LA  - eng
PT  - Journal Article
DEP - 20230721
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Limonins)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Lipopolysaccharides/pharmacology
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Limonins/pharmacology/therapeutic use
MH  - NF-E2-Related Factor 2/metabolism
MH  - *Acute Lung Injury/chemically induced/drug therapy/metabolism
MH  - Lung/pathology
MH  - Inflammation/pathology
MH  - Mice, Inbred C57BL
OTO - NOTNLM
OT  - AMPKalpha
OT  - Acute lung injury
OT  - Limonin
OT  - Macrophage
OT  - NRF2
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/07/24 00:41
MHDA- 2023/08/25 06:42
CRDT- 2023/07/23 18:03
PHST- 2023/05/22 00:00 [received]
PHST- 2023/07/05 00:00 [revised]
PHST- 2023/07/18 00:00 [accepted]
PHST- 2023/08/25 06:42 [medline]
PHST- 2023/07/24 00:41 [pubmed]
PHST- 2023/07/23 18:03 [entrez]
AID - S1567-5769(23)01003-2 [pii]
AID - 10.1016/j.intimp.2023.110678 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Sep;122:110678. doi: 10.1016/j.intimp.2023.110678. Epub 
      2023 Jul 21.