title: Procyanidin B2 inhibits NLRP3 inflammasome activation in human vascular endothelial cells.
abstract: Procyanidins are the flavanols from polyphenols commonly found in fruits and red wine. Recent studies have shown that procyanidins possess potential anti-inflammatory activities. However, underlying mechanisms remain to be understood. Inflammasomes are multi-protein complexes composed of pro-caspase and pattern recognition receptors (PRRs) such as NOD-like receptor family, pyrin domain containing 3 (NLRP3). Since aberrant activation of NLRP3 inflammasome is implicated in the pathogeneses of pro-inflammatory diseases such as diabetes, atherosclerosis and arthritis, we aimed to investigate whether procyanidin B2 (PCB2), the most widely distributed natural procyanidins, inhibits the activation of NLRP3 inflammasome in endothelial cells (ECs). We found that, in human umbilical vein ECs (HUVECs), PCB2 significantly suppressed the activation of NLRP3 inflammasome and inhibited subsequent caspase-1 activation and interleukin (IL)-1β secretion in response to lipopolysaccharides (LPS). PCB2 negatively regulated the gene expression of NLRP3. In addition, PCB2 attenuated LPS-induced production of reactive oxygen species (ROS) and the transcriptional activity of activator protein-1 (AP-1). In conclusion, we demonstrated for the first time that procyanidin B2 inhibits NLRP3 inflammasome activation via suppression of AP-1 pathway in ECs. These results suggest a new mechanism by which natural flavoids such as procyanidins exert their vascular protective effects.
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China; School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China; Nutrition and Food Safety Engineering Research Center of Shaanxi Province, Xi'an, 710061, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China; School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Ni
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China; Institute of Cardiovascular Science, Peking University, Beijing, 100191, China. Electronic address: nanpingwang2003@yahoo.com.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D044946:Biflavonoids / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D002392:Catechin / Q000494:pharmacology*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016133:Polymerase Chain Reaction; D044945:Proanthocyanidins / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics
chemical_list: D044946:Biflavonoids; D002352:Carrier Proteins; D017931:DNA Primers; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D044945:Proanthocyanidins; D016755:Proto-Oncogene Proteins c-jun; C479580:procyanidin B2; D002392:Catechin
keywords: AP-1; NLRP3 inflammasome; Procyanidin B2; ROS