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|Title:||Modulating effect of luteolin on ethanol and cerulein induced inflammation— In silico and in vivo studies using rat model of pancreatitis|
Kripa, Kavasseri Ganesan
|Abstract:||NLRP3 inflammasomes are induced in pancreas during inflammatory insult, which contain caspase activation and recruitment domain (CARD) and pyrin domain (PYD) of apoptosis associated speck-like protein containing a CARD (ASC). It is known that NLRP3-ASC interaction via PYD domain recruits and activate caspase-1. Through CARD, ASC brings monomers of procaspase-1 into close proximity and activate them which in turn activate pro-inflammatory cytokines. The assembly of inflammasome and activation of procaspase-1 is thought to be the molecular target for anti-inflammatory drugs. Here, we investigated the molecular interactions of luteolin, a potent anti-inflammatory agent with procaspase-1, ASC-CARD and ASC-PYD using Acceryls Discovery Studio Visualizer. To assess the pancreato-protective effect of luteolin, rats were administered with ethanol (36% of total calories for five weeks) and cerulein (20 µg/kg body wt. i.p., weekly thrice for last three weeks). In addition, a group of rats also received 2 mg luteolin/kg body wt. orally from third week till the experimental period. Co-administration of luteolin reduced the levels of pancreatic and inflammatory marker enzymes in serum and maintained the antioxidant status in pancreas. Immunohistochemical analysis confirmed the presence of ASC protein in excess in the pancreas of ethanol-cerulein administered rats than in rats co-administered with luteolin. Luteolin satisfies Lipinski’s rule of five to determine the drug likeness property. The energy value and the hydrophobic interactions obtained in the present docking study confirmed that there was a strong binding affinity of luteolin towards procaspase-1, ASC-CARD, ASC-PYD that might interfere with the molecular assembly of NLRP3 inflammasome and the production of pro-inflammatory cytokines.|
|ISSN:||0975-1009 (Online); 0019-5189 (Print)|
|Appears in Collections:||IJEB Vol.57(07) [July 2019]|
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