title: Quercetin, luteolin and epigallocatechin gallate alleviate TXNIP and NLRP3-mediated inflammation and apoptosis with regulation of AMPK in endothelial cells.
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.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing, China.
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing, China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing, China. Electronic address: liukangxyz@gmail.com.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019332:Endothelin-1 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D047311:Luteolin / Q000494:pharmacology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D019332:Endothelin-1; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D047428:Protein Kinase Inhibitors; C486715:TXNIP protein, human; D019308:Palmitic Acid; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D055372:AMP-Activated Protein Kinases; D047311:Luteolin
keywords: Endoplasmic reticulum stress; Endothelial cells; Flavonoids; NLRP3; TXNIP