title: Thymoquinone ameliorates NLRP3-mediated inflammation in the pancreas of albino Wistar rats fed ethanol and high-fat diet.
abstract: BACKGROUND
  Inflammasomes are protein complexes that mediate the process of inflammation and tissue injury by regulating the level of cytokine production. Pancreatitis is a major gastrointestinal disorder characterized by painful inflammation in the pancreas. The aim of this study was to evaluate whether thymoquinone (TQ) exerts anti-inflammatory activity by influencing the expression of the apoptosis-associated speck-like protein (ASC) complex of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes in rats subjected to experimental pancreatitis.
  
  
  METHODS
  Male albino Wistar rats were randomly separated into four groups. Rats in groups 1 and 2 were fed with a normal diet for 90 days, and rats in groups 3 and 4 were administered with ethanol (EtOH) 8-12 g/kg/day orally and fed with a high-fat diet (HFD) for 90 days. In addition, rats in groups 2 and 4 were administered with 100 mg/kg body weight of TQ from the 31st day. The serum lipase (L)/amylase (A) ratio; the oxidative stress markers; the GSH/GSSG ratio; the mRNA expression of ASC, caspase-1, IL-1β, IL-18, and TNF-α; and the protein expression of ASC and caspase-1 in the pancreas were assessed.
  
  
  RESULTS
  We observed a significant increase in the serum L/A ratio and oxidative stress, a decrease in the GSH/GSSG ratio, and a GST activity in EtOH- and HFD-fed rats. The mRNA expression of IL-1β, IL-18, and TNF-α was significantly reduced in TQ-coadministered rats than that in EtOH- and HFD-fed rats. The upregulation of mRNA and the protein expression of ASC and caspase-1 were significantly reduced in TQ-coadministered rats.
  
  
  CONCLUSIONS
  TQ exerts the anti-inflammatory activity probably by downregulating the ASC expression to minimize the maturation of proinflammatory cytokines.
authors.forename: Suguna
authors.initials: S
authors.lastname: Periyanayagam
authors.forename: Geetha
authors.initials: G
authors.lastname: Arumugam
authors.forename: Aruna
authors.initials: A
authors.lastname: Ravikumar
authors.forename: Vijaiyan Siva
authors.initials: VS
authors.lastname: Ganesan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D016227:Benzoquinones / Q000494:pharmacology*; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress / Q000187:drug effects; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D016227:Benzoquinones; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; C498535:Pycard protein, rat; D012333:RNA, Messenger; D000431:Ethanol; D020170:Caspase 1; C003466:thymoquinone