PMID- 36751854 OWN - NLM STAT- MEDLINE DCOM- 20230413 LR - 20230413 IS - 1099-1573 (Electronic) IS - 0951-418X (Linking) VI - 37 IP - 4 DP - 2023 Apr TI - Narirutin exerts anti-inflammatory activity by inhibiting NLRP3 inflammasome activation in macrophages. PG - 1293-1308 LID - 10.1002/ptr.7686 [doi] AB - 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)-1beta and pyroptosis in lipopolysaccharide (LPS)/ATP-stimulated macrophages. Narirutin decreased the expression of NLRP3 and IL-1beta in the LPS-priming step through inhibition of NF-kappaB, 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. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Ri, Myong Hak AU - Ri MH AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. AD - Faculty of Life Science, Kim Il Sung University, Pyongyang, Democratic People's Republic of Korea. FAU - Li, Ming Yue AU - Li MY AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. FAU - Xing, Yue AU - Xing Y AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. FAU - Zuo, Hong Xiang AU - Zuo HX AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. FAU - Li, Guangyi AU - Li G AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. FAU - Li, Chengcheng AU - Li C AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. FAU - Ma, Juan AU - Ma J AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. FAU - Jin, Xuejun AU - Jin X AUID- ORCID: 0000-0001-6998-2602 AD - Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China. LA - eng GR - 81760657/National Natural Science Foundation of China/ GR - 602021041/Yanbian University Doctoral Research Fund Project/ GR - YDZJ2022101ZYTS180/The Jilin Province Science and Technology Development Plan Project/ GR - YDZJ202201ZYTS169/The Jilin Province Science and Technology Development Plan Project/ GR - YDZJ202201ZYTS272/The Jilin Province Science and Technology Development Plan Project/ GR - JJKH20220561KJ/the Education Department of Jilin Province Project/ GR - ydbq202113/Yanbian University Doctoral Research Fund Project/ GR - ydbq202216/Yanbian University Doctoral Research Fund Project/ GR - 111Project,D18012/the Higher Education Discipline Innovation Project/ PT - Journal Article DEP - 20230207 PL - England TA - Phytother Res JT - Phytotherapy research : PTR JID - 8904486 RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 06M5EAT0YC (narirutin) RN - 0 (NLR Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (Flavanones) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Nlrp3 protein, mouse) SB - IM MH - Animals MH - Mice MH - Inflammasomes MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - NLR Proteins/metabolism MH - Lipopolysaccharides/pharmacology MH - Macrophages MH - *Flavanones/pharmacology MH - *Colitis/chemically induced MH - Inflammation/metabolism MH - Anti-Inflammatory Agents/pharmacology MH - *Peritonitis/metabolism OTO - NOTNLM OT - DSS-induced colitis OT - NLRP3 inflammasome OT - alum-induced peritonitis OT - citrus peel OT - inflammation OT - narirutin EDAT- 2023/02/09 06:00 MHDA- 2023/04/13 06:42 CRDT- 2023/02/08 02:42 PHST- 2022/10/18 00:00 [revised] PHST- 2022/07/30 00:00 [received] PHST- 2022/10/27 00:00 [accepted] PHST- 2023/04/13 06:42 [medline] PHST- 2023/02/09 06:00 [pubmed] PHST- 2023/02/08 02:42 [entrez] AID - 10.1002/ptr.7686 [doi] PST - ppublish SO - Phytother Res. 2023 Apr;37(4):1293-1308. doi: 10.1002/ptr.7686. Epub 2023 Feb 7.