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Quercetin, luteolin and epigallocatechin gallate alleviate TXNIP and NLRP3-mediated inflammation and apoptosis with regulation of AMPK in endothelial cells.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2014 Dec 15; Vol. 745, pp. 59-68. Date of Electronic Publication: 2014 Oct 14. - Publication Year :
- 2014
-
Abstract
- Endoplasmic reticulum stress (ER stress)-associated thioredoxin-interacting protein (TXNIP) and NOD-like receptor pyrin domain containing-3 (NLRP3) signaling is a key event in the endothelial dysfunction. It induces the IL-1β production and thus accounts for inflammation and cell death. Quercetin, luteolin and epigallocatechin gallate (EGCG) are flavonoids with beneficial effects on cardiovascular functions, and we wondered whether these flavonoids protect endothelial functions against ER stress-associated impairments. Palmitate stimulation evoked oxidative stress and then induced TXNIP and NLRP3 inflammasome activation in the endothelial cells. Quercetin, luteolin and EGCG reduced reactive oxygen species production and inhibited TXNIP and NLRP3 inflammasome activation, lead to the downregulation of IL-1β expression. Meanwhile, these agents protected cells from apoptosis by restoration of mitochondrial membrane potential (Δψm) and inhibition of caspase-3 activity. PA stimulation induced inflammation accompanied by the loss of NO production in endothelial cells, but these alterations were reversed by treatment with quercetin, luteolin and EGCG. Co-treatment with AMPK inhibitor compound C diminished the beneficial effects of these flavonoids, suggesting the involvement of AMPK. In conclusion, quercetin, luteolin and EGCG inhibited ER stress-associated TXNIP and NLRP3 inflammasome activation, and thereby protected endothelial cells from inflammatory and apoptotic damage.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- AMP-Activated Protein Kinases antagonists & inhibitors
Apoptosis physiology
Catechin pharmacology
Cell Line
Endoplasmic Reticulum Stress drug effects
Endothelial Cells drug effects
Endothelial Cells pathology
Endothelial Cells physiology
Endothelin-1 genetics
Gene Expression drug effects
Human Umbilical Vein Endothelial Cells
Humans
Inflammasomes drug effects
Inflammation etiology
Inflammation physiopathology
Luteolin pharmacology
NLR Family, Pyrin Domain-Containing 3 Protein
Oxidative Stress drug effects
Palmitic Acid pharmacology
Protein Kinase Inhibitors pharmacology
Quercetin pharmacology
AMP-Activated Protein Kinases metabolism
Apoptosis drug effects
Carrier Proteins physiology
Catechin analogs & derivatives
Inflammation prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 745
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 25446924
- Full Text :
- https://doi.org/10.1016/j.ejphar.2014.09.046