title: Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis.
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.
authors: Department of Biochemistry, Bharathi Women's College, Affiliated to University of Madras, Broadway, Chennai, 600 108, Tamil Nadu, India.
authors: Ravikumar
authors: R
authors: Aruna
authors: Arumugam
authors: A
authors: Geetha
authors: Periyanayagam
authors: P
authors: Suguna
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002108:Ceruletide / Q000633:toxicity; D004195:Disease Models, Animal; D004798:Enzymes / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress / Q000187:drug effects; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012431:Rutin / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D004798:Enzymes; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; C498535:Pycard protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D000431:Ethanol; D012431:Rutin; D002108:Ceruletide; D020170:Caspase 1; D005978:Glutathione