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  • Title: Thymoquinone ameliorates NLRP3-mediated inflammation in the pancreas of albino Wistar rats fed ethanol and high-fat diet.
    Author: Periyanayagam S, Arumugam G, Ravikumar A, Ganesan VS.
    Journal: J Basic Clin Physiol Pharmacol; 2015 Nov; 26(6):623-32. PubMed ID: 25719309.
    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.
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