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.

TQ exerts the anti-inflammatory activity probably by downregulating the ASC expression to minimize the maturation of proinflammatory cytokines.

The present study investigated the effect of rutin, a natural flavonoid, on the expression of caspase activation recruitment domain (CARD) and pyrin domain (PYD) of apoptosis-associated speck-like protein (ASC), a mediator of inflammation, in the pancreas of rats administered with ethanol (EtOH) and high-fat diet (HFD). Pancreatitis was induced in male albino Wistar rats by administering EtOH (8–12 g/kg/day) and HFD (22% fat) for 90 days. In addition, rats also received 100 mg rutin/kg body weight orally from 31st day till the experimental period. Serum levels of cytokines, interleukin 18 (IL-18) and IL-6; activity levels of caspase-1 and myeloperoxidase (MPO); messenger RNA (mRNA) expression of tumor necrosis factor α (TNF-α), caspase-1, CARD and PYD of ASC; and histological changes in pancreas were assessed. We observed a significant elevation in serum IL-18, IL-6, caspase-1 and MPO activities, mRNA expression of PYD, TNF-α and caspase-1 in the pancreas of rats administered with EtOH and HFD. Rutin administration along with EtOH and HFD significantly upregulated the mRNA expression of CARD and downregulated PYD, caspase-1, and TNF-α expressions. Rutin supplementation was also found to reduce IL-18 and IL-6 levels; and inflammatory changes in tissue architecture were evidenced by histological observations. The anti-inflammatory activity of rutin might be due to its effect on modulating the expression of ASC complex that mediates inflammation.

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