JunYuan Zheng1, JiangHong Wu1, Jing Chen1, Jie Liu1, YingYing Lu1, ChunLan Huang1, GuoYong Hu1, XingPeng Wang1, Yue Zeng2. 1. Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. 2. Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: zengyue1592@yahoo.com.
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.
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.