Quercetin, luteolin and epigallocatechin gallate alleviate TXNIP and NLRP3-mediated inflammation and apoptosis with regulation of AMPK in endothelial cells

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-1 beta 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 NERP3 inflammasome activation in the endothelial cells. Quercelin, luleolin and EGCG reduced reactive oxygen species production and inhibited TXNIP and NLRP3 inflammasome activation, lead to the down regulation of IL-1 beta expression. Meanwhile, these agents protected cells from apoplosis by restoration of milochonclrial membrane potential (Delta psi m) 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 quercelin, luleolin 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 NERP3 inflammasome activation, and thereby protected endothelial cells from inflammatory and apoptotic damage. (C) 2014 Elsevier B.V. All rights reserved.