Paeonol protects against acute pancreatitis by inhibiting M1 macrophage polarization via the NLRP3 inflammasomes pathway

• Published in: Biochemical and biophysical research communications 2022-04, Vol.600, p.35-43
• Main Authors: Yuan, Chenchen, Xu, Xingmeng, Wang, Ningzhi, Zhu, Qingtian, Zhang, Junxian, Gong, Weijuan, Ding, Yanbing, Xiao, Weiming, Chen, Weiwei, Lu, Guotao, Yao, Guanghuai, Pan, Jiajia, Wu, Keyan
• Format: Article
• Language: English
• Subjects: Acetophenones; Acute Disease; Acute pancreatitis; Animals; Ceruletide - pharmacology; Inflammasomes - metabolism; Inflammation; Macrophage polarization; Macrophages - metabolism; MCC950; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasomes; Paeonol; Pancreatitis - chemically induced; Pancreatitis - drug therapy; Reactive Oxygen Species - adverse effects
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.02.019

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-1β 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 (ΔΨm), 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. •Paeonol alleviates pancreatic injury and inflammatory response in vivo and vitro acute pancreatitis models.•Paeonol inhibits M1 macrophage polarization and down-regulate the NLRP3 inflammasomes pathway.•Paeonol may be a therapeutic candidate for acute pancreatitis in clinical.