Narirutin exerts anti-inflammatory activity by inhibiting NLRP3 inflammasome activation in macrophages.
Myong Hak RiMing Yue LiYue XingHong Xiang ZuoGuangyi LiChengcheng LiJuan MaXuejun JinPublished in: Phytotherapy research : PTR (2023)
Citrus 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.
Keyphrases
- nlrp inflammasome
- signaling pathway
- pi k akt
- inflammatory response
- anti inflammatory
- oxidative stress
- lps induced
- cell proliferation
- mouse model
- epithelial mesenchymal transition
- poor prognosis
- metabolic syndrome
- cell death
- physical activity
- diabetic rats
- endothelial cells
- high glucose
- mesenchymal stem cells
- immune response
- nuclear factor
- endoplasmic reticulum stress
- high fat diet induced