Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis

Mol Cell Biochem. 2014 Nov;396(1-2):269-80. doi: 10.1007/s11010-014-2162-8. Epub 2014 Jul 25.

Abstract

Inflammasomes are protein complexes formed in response to tissue injury and inflammation to regulate the formation of proinflammatory cytokines. Nod-like receptor pyrin domain containing 3 (NLRP3) is one such inflammasome involved in pancreatic inflammation. Caspase activation recruitment domain (CARD) is an interaction motif found in all the major components of NLRP3 inflammasome such as apoptosis associated speck-like CARD containing protein (ASC) and procaspase-1. NLRP3 activates procaspase-1 with the concerted action of CARD domain of ASC. In the present study, the effect of rutin, a natural flavonoid on the expression of ASC of NLRP3, was investigated in rats treated with ethanol (EtOH) and cerulein (Cer). Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats were fed normal diet, whereas groups 3 and 4 rats were fed EtOH (36 % of total calories) containing diet for a total period of 5 weeks and also administered Cer (20 µg/kg body weight i.p.) thrice weekly for the last 3 weeks. In addition, groups 2 and 4 rats received daily 100 mg/kg body weight of rutin from third week. Rutin co-administration significantly decreased the level of pancreatic marker enzymes, oxidative stress markers, inflammatory markers, mRNA expression of caspase-1, cytokines, ASC-NLRP3, and protein expression of caspase-1 and ASC in rats received EtOH-Cer. The results of the study revealed that rutin can reduce inflammation in pancreas probably by influencing the down regulation of ASC-NLRP3 which might result in the reduced activation of caspase-1 and controlled cytokine production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / metabolism
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Biomarkers / metabolism
  • CARD Signaling Adaptor Proteins
  • Carrier Proteins
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Ceruletide / toxicity
  • Disease Models, Animal
  • Enzymes / metabolism
  • Ethanol / toxicity
  • Glutathione / metabolism
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Oxidative Stress / drug effects
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Pancreatitis / metabolism
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Rutin / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • CARD Signaling Adaptor Proteins
  • Carrier Proteins
  • Enzymes
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Pycard protein, rat
  • Receptors, Cytoplasmic and Nuclear
  • Ethanol
  • Rutin
  • Ceruletide
  • Caspase 1
  • Glutathione