Luteolin ameliorates LPS-induced acute liver injury by inhibiting TXNIP-NLRP3 inflammasome in mice.
Animals
Carrier Proteins
/ antagonists & inhibitors
Cell Death
/ drug effects
Chemical and Drug Induced Liver Injury
/ drug therapy
Hepatitis
/ drug therapy
Hepatocytes
/ drug effects
Inflammasomes
/ drug effects
Lipopolysaccharides
/ toxicity
Luteolin
/ pharmacology
Male
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein
/ antagonists & inhibitors
Oxidative Stress
/ drug effects
Protective Agents
/ pharmacology
Thioredoxins
/ antagonists & inhibitors
Acute liver injury
Inflammation
Luteolin
NLRP3
TXNIP
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
12
11
2020
revised:
17
04
2021
accepted:
27
04
2021
pubmed:
28
5
2021
medline:
7
7
2021
entrez:
27
5
2021
Statut:
ppublish
Résumé
Chemical liver injury is one of the main causes of acute liver failure and death. To date, however, treatment strategies for acute liver injury have been limited. Therefore, there is an urgent need to find new therapeutic targets and effective drugs. NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a complex of multiple proteins that has been shown to induce cell death under inflammatory and stress pathologic conditions and is thought to provide new targets for the treatment of a variety of diseases. The purpose of this study was to investigate whether luteolin has a protective effect on the liver and further elucidate whether it is realized through the thioredoxin interacting protein (TXNIP)-NLRP3 axis. Acute hepatic injury in mice caused by intraperitoneal injection of lipopolysaccharide (LPS) was treated with or without luteolin. Male C57BL/6 mice and mouse primary hepatocytes were selected. TXNIP protein knockdown was achieved by siRNA, qPCR and Western blot were performed to explore the mechanism of luteolin in alleviating acute liver injury. The results indicated that luteolin had a markedly protective effect on acute liver injury induced by LPS in mice by inhibiting the TXNIP-NLRP3 axis. Luteolin inhibits NLRP3 inflammasome activation by suppressing TXNIP, apoptosis associated speck-like protein containing a CARD domain (ASC), caspase-1, interleukin-1β (IL-1β) and IL-18 to reduce liver injury. In addition, luteolin inhibits LPS-induced liver inflammation by inhibiting the production of inflammation-related gene tumor necrosis factor-α (TNF-α), IL-10, and IL-6. What's more, luteolin alleviated LPS-induced hepatocyte injury by inhibiting oxidative stress and regulating MDA, SOD, and GSH levels. However, the protective effect of luteolin on acute LPS-induced liver injury in mice was blocked by si-TXNIP in vitro. These combined data showed that luteolin may alleviate LPS-induced liver injury through the TXNIP-NLPR3 axis, providing new therapeutic targets and therapeutic drugs for subsequent studies.
Sections du résumé
BACKGROUND
BACKGROUND
Chemical liver injury is one of the main causes of acute liver failure and death. To date, however, treatment strategies for acute liver injury have been limited. Therefore, there is an urgent need to find new therapeutic targets and effective drugs. NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a complex of multiple proteins that has been shown to induce cell death under inflammatory and stress pathologic conditions and is thought to provide new targets for the treatment of a variety of diseases.
PURPOSE
OBJECTIVE
The purpose of this study was to investigate whether luteolin has a protective effect on the liver and further elucidate whether it is realized through the thioredoxin interacting protein (TXNIP)-NLRP3 axis.
STUDY DESIGN
METHODS
Acute hepatic injury in mice caused by intraperitoneal injection of lipopolysaccharide (LPS) was treated with or without luteolin.
METHODS
METHODS
Male C57BL/6 mice and mouse primary hepatocytes were selected. TXNIP protein knockdown was achieved by siRNA, qPCR and Western blot were performed to explore the mechanism of luteolin in alleviating acute liver injury.
RESULTS
RESULTS
The results indicated that luteolin had a markedly protective effect on acute liver injury induced by LPS in mice by inhibiting the TXNIP-NLRP3 axis. Luteolin inhibits NLRP3 inflammasome activation by suppressing TXNIP, apoptosis associated speck-like protein containing a CARD domain (ASC), caspase-1, interleukin-1β (IL-1β) and IL-18 to reduce liver injury. In addition, luteolin inhibits LPS-induced liver inflammation by inhibiting the production of inflammation-related gene tumor necrosis factor-α (TNF-α), IL-10, and IL-6. What's more, luteolin alleviated LPS-induced hepatocyte injury by inhibiting oxidative stress and regulating MDA, SOD, and GSH levels. However, the protective effect of luteolin on acute LPS-induced liver injury in mice was blocked by si-TXNIP in vitro.
CONCLUSIONS
CONCLUSIONS
These combined data showed that luteolin may alleviate LPS-induced liver injury through the TXNIP-NLPR3 axis, providing new therapeutic targets and therapeutic drugs for subsequent studies.
Identifiants
pubmed: 34044253
pii: S0944-7113(21)00128-8
doi: 10.1016/j.phymed.2021.153586
pii:
doi:
Substances chimiques
Carrier Proteins
0
Inflammasomes
0
Lipopolysaccharides
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, mouse
0
Protective Agents
0
Txnip protein, mouse
0
Thioredoxins
52500-60-4
Luteolin
KUX1ZNC9J2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153586Informations de copyright
Copyright © 2021 Elsevier GmbH. All rights reserved.