Therapeutic effects of quercetin on early inflammation in hypertriglyceridemia-related acute pancreatitis and its mechanism.

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.