PMID- 35988521
OWN - NLM
STAT- MEDLINE
DCOM- 20220914
LR  - 20220914
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 111
DP  - 2022 Oct
TI  - Eupalinolide B attenuates lipopolysaccharide-induced acute lung injury through 
      inhibition of NF-kappaB and MAPKs signaling by targeting TAK1 protein.
PG  - 109148
LID - S1567-5769(22)00632-4 [pii]
LID - 10.1016/j.intimp.2022.109148 [doi]
AB  - Acute lung injury (ALI) is a life-threatening disease characterized by severe 
      inflammatory response, which has no pharmacological therapy in clinic. In this 
      study, we found that eupalinolide B (EB), a sesquiterpene lactone isolated from 
      Eupatorium lindleyanum, significantly ameliorated lipopolysaccharide 
      (LPS)-induced ALI in mice, which manifests as reduction in lung injury score, 
      activity of myeloperoxidase, and release of cytokines interleukin (IL)-1beta, IL-6, 
      tumor necrosis factor-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1). 
      In RAW264.7 murine macrophages, EB effectively inhibited LPS-induced production 
      of nitric oxide (NO) and prostaglandin E2 (PGE(2)) by down-regulating the 
      expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), 
      respectively. Mechanistically, EB not only blocked LPS-induced phosphorylation of 
      inhibitor of nuclear factor kappa B kinase-alpha/beta (IKKalpha/beta), phosphorylation and 
      degradation of inhibitor of nuclear factor-kappa B alpha (IkappaBalpha), and 
      phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) P65, 
      but also suppressed LPS-induced phosphorylation of mitogen-activated protein 
      kinases (MAPKs) in vitro or in vivo. Through cellular thermal shift assay and 
      western blotting, EB was demonstrated to target and inactivate transforming 
      growth factor beta activated kinase-1 (TAK1), which is an important upstream kinase 
      for the activation of NF-kappaB and MAPKs pathways. Additionally, EB-mediated actions 
      were markedly abolished by dithiothreitol in LPS-exposed RAW264.7 cells, 
      suggesting a crucial role of the alpha,gamma-unsaturated lactone for the 
      anti-inflammatory activity of EB. In conclusion, our findings showed that EB 
      could effectively alleviate ALI in mice, and attenuate inflammatory response by 
      inhibiting the activation of TAK1, and TAK1-mediated activation of NF-kappaB and 
      MAPKs cascades.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Yang, Luyao
AU  - Yang L
AD  - Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, 
      China; College of Medical Technology, Chengdu University of Traditional Chinese 
      Medicine, Chengdu 611137, China.
FAU - Chen, Hongqing
AU  - Chen H
AD  - Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, 
      China; College of Medical Technology, Chengdu University of Traditional Chinese 
      Medicine, Chengdu 611137, China.
FAU - Hu, Qiongying
AU  - Hu Q
AD  - Department of Laboratory Medicine, Hospital of Chengdu University of Traditional 
      Chinese Medicine, Chengdu 610072, China.
FAU - Liu, Lu
AU  - Liu L
AD  - College of Pharmacy, Chengdu University of Traditional Chinese Medicine, 611137 
      Chengdu, China.
FAU - Yuan, Yun
AU  - Yuan Y
AD  - Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, 
      China; College of Medical Technology, Chengdu University of Traditional Chinese 
      Medicine, Chengdu 611137, China.
FAU - Zhang, Chuantao
AU  - Zhang C
AD  - Department of Respiratory Medicine, Hospital of Chengdu University of Traditional 
      Chinese Medicine, 610072 Chengdu, China.
FAU - Tang, Jianyuan
AU  - Tang J
AD  - Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, 
      China. Electronic address: tangjianyuan163@163.com.
FAU - Shen, Xiaofei
AU  - Shen X
AD  - Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, 
      China. Electronic address: sxfcd2008@163.com.
LA  - eng
PT  - Journal Article
DEP - 20220818
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Lactones)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Sesquiterpenes, Germacrane)
RN  - 0 (eupalinolide B)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - *Acute Lung Injury/chemically induced/drug therapy
MH  - Animals
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/metabolism
MH  - Lactones/pharmacology/therapeutic use
MH  - *Lipopolysaccharides
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Sesquiterpenes, Germacrane
OTO - NOTNLM
OT  - Acute lung injury
OT  - Eupalinolide B
OT  - Lipopolysaccharide
OT  - Macrophages
OT  - NF-kappaB and MAPKs
OT  - TAK1
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- 2022/08/22 06:00
MHDA- 2022/09/15 06:00
CRDT- 2022/08/21 18:30
PHST- 2022/04/23 00:00 [received]
PHST- 2022/07/19 00:00 [revised]
PHST- 2022/08/07 00:00 [accepted]
PHST- 2022/08/22 06:00 [pubmed]
PHST- 2022/09/15 06:00 [medline]
PHST- 2022/08/21 18:30 [entrez]
AID - S1567-5769(22)00632-4 [pii]
AID - 10.1016/j.intimp.2022.109148 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2022 Oct;111:109148. doi: 10.1016/j.intimp.2022.109148. Epub 
      2022 Aug 18.