PMID- 35182973 OWN - NLM STAT- MEDLINE DCOM- 20220411 LR - 20220411 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 600 DP - 2022 Apr 16 TI - Paeonol protects against acute pancreatitis by inhibiting M1 macrophage polarization via the NLRP3 inflammasomes pathway. PG - 35-43 LID - S0006-291X(22)00201-7 [pii] LID - 10.1016/j.bbrc.2022.02.019 [doi] AB - The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1beta and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (DeltaPsim), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Yuan, Chenchen AU - Yuan C AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Xu, Xingmeng AU - Xu X AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Wang, Ningzhi AU - Wang N AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Zhu, Qingtian AU - Zhu Q AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Zhang, Junxian AU - Zhang J AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Gong, Weijuan AU - Gong W AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Ding, Yanbing AU - Ding Y AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Xiao, Weiming AU - Xiao W AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Chen, Weiwei AU - Chen W AD - Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China. FAU - Lu, Guotao AU - Lu G AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. FAU - Yao, Guanghuai AU - Yao G AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. Electronic address: ghyao@yzu.edu.cn. FAU - Pan, Jiajia AU - Pan J AD - Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China; Department of Intensive Care Unit, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. Electronic address: jjpan@yzu.edu.cn. FAU - Wu, Keyan AU - Wu K AD - Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China. Electronic address: kywu@yzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220208 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Acetophenones) RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Reactive Oxygen Species) RN - 3R834EPI82 (paeonol) RN - 888Y08971B (Ceruletide) SB - IM MH - Acetophenones MH - Acute Disease MH - Animals MH - Ceruletide/pharmacology MH - *Inflammasomes/metabolism MH - Macrophages/metabolism MH - Mice MH - Mice, Inbred C57BL MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - *Pancreatitis/chemically induced/drug therapy MH - Reactive Oxygen Species/adverse effects OTO - NOTNLM OT - Acute pancreatitis OT - Inflammation OT - MCC950 OT - Macrophage polarization OT - NLRP3 inflammasomes OT - Paeonol COIS- Declaration of competing interest All authors of this paper have no conflict of interests to disclose. EDAT- 2022/02/20 06:00 MHDA- 2022/04/12 06:00 CRDT- 2022/02/19 20:14 PHST- 2021/12/14 00:00 [received] PHST- 2022/02/04 00:00 [revised] PHST- 2022/02/07 00:00 [accepted] PHST- 2022/02/20 06:00 [pubmed] PHST- 2022/04/12 06:00 [medline] PHST- 2022/02/19 20:14 [entrez] AID - S0006-291X(22)00201-7 [pii] AID - 10.1016/j.bbrc.2022.02.019 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2022 Apr 16;600:35-43. doi: 10.1016/j.bbrc.2022.02.019. Epub 2022 Feb 8.