Narirutin exerts anti‐inflammatory activity by inhibiting NLRP3 inflammasome activation in macrophages

Abstract

AbstractCitrus peel has long been used in traditional medicine in Asia to treat common cold, dyspepsia, cough, and phlegm. Narirutin–a flavanone‐7‐O‐glycoside–is the major flavonoid in citrus peel, and has anti‐oxidative, anti‐allergic, and anti‐inflammatory activities. However, the anti‐inflammatory mechanism of narirutin has not been fully elucidated. This study is aimed to investigate the effects of narirutin on the Nod‐like receptor protein 3 (NLRP3)‐mediated inflammatory response in vitro and in vivo, and determine the underlying mechanism. THP‐1 differentiated macrophages and bone marrow‐derived macrophages (BMDMs) were used for in vitro experiments, while dextran sulfate sodium (DSS)‐induced colitis and alum‐induced peritonitis mouse models were constructed to test inflammation in vivo. Narirutin suppressed secretion of interleukin (IL)‐1β and pyroptosis in lipopolysaccharide (LPS)/ATP‐stimulated macrophages. Narirutin decreased the expression of NLRP3 and IL‐1β in the LPS‐priming step through inhibition of NF‐κB, MAPK and PI3K /AKT signaling pathways. Narirutin inhibited NLRP3–ASC interaction to suppress NLRP3 inflammasome assembly. Furthermore, oral administration of narirutin (300 mg/kg) alleviated inflammation symptoms in mice with peritonitis and colitis. These results suggest that narirutin exerts its anti‐inflammatory activity by suppressing NLRP3 inflammasome activation via inhibition of the NLRP3 inflammasome priming processes and NLRP3–ASC interaction in macrophages.