title: Therapeutic effects of quercetin on early inflammation in hypertriglyceridemia-related acute pancreatitis and its mechanism.
abstract: OBJECTIVE
  To investigate the therapeutic effects of quercetin on early-stage inflammation in hypertriglyceridemia (HTG)-related acute pancreatitis (AP) both in vivo and in vitro, and its possible mechanism.
  
  
  METHODS
  In vivo, rats were fed a high-fat diet to induce HTG, and AP was induced by intraperitoneal injection of cerulein (50 μg/kg × 2). Quercetin (100, 150 and 200 mg/kg) was administered by intraperitoneal injection after AP induction. In vitro, rat exocrine acinar cells were preincubated with palmitic acid (PA, 0.1 mmol/L, 6 h) with quercetin (5, 10, 20 and 40 μM) prior to a cholecystokinin analog CCK-8 (20pM). Injury of the pancreas was assessed by amylase secretion and pancreatic histological evaluation. Inflammation was estimated by measuring IL-1β, IL-6, TNFα and NF-kB expression. Dynamic expression of IRE1α, sXBP1, C/EBPα and C/EBPβ was monitored by real-time PCR, immunofluorescence (IF) and western blot (WB).
  
  
  RESULTS
  Quercetin intervention reduced plasma amylase level (P < 0.001) in a dose-dependent manner, attenuated pancreatic histopathological damage (P < 0.05), and reduced the mRNA and protein expression of NF-kB, IL-1β, IL-6, TNFα (P < 0.05) more significantly in HTG-related AP rats than in normal-lipid AP rats. Quercetin also down-regulated gene and protein expression levels of IRE1α, sXBP1, C/EBPα and C/EBPβ in a dose-dependent manner.
  
  
  CONCLUSIONS
  Quercetin attenuates early-stage inflammation in HTG-related AP, probably by reducing IRE1α, sXBP1, C/EBPα and C/EBPβ expression.
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: JunYuan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: JiangHong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: YingYing
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: ChunLan
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: GuoYong
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: XingPeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: zengyue1592@yahoo.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D015228:Hypertriglyceridemia / Q000150:complications*; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004041:Dietary Fats; D011794:Quercetin
keywords: Acute pancreatitis; C/EBPs; Endoplasmic reticulum stress; Hypertriglyceridemia; Pancreatic acinar cells; Quercetin