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

Chenchen Yuan; Xingmeng Xu; Ningzhi Wang; Qingtian Zhu; Junxian Zhang; Weijuan Gong; Yanbing Ding; Weiming Xiao; Weiwei Chen; Guotao Lu; Guanghuai Yao; Jiajia Pan; Keyan Wu

doi:10.1016/j.bbrc.2022.02.019

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

Biochem Biophys Res Commun. 2022 Apr 16:600:35-43. doi: 10.1016/j.bbrc.2022.02.019. Epub 2022 Feb 8.

Authors

Affiliations

¹ 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.
² Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
³ 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.
⁴ 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.
⁵ 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.

PMID: 35182973
DOI: 10.1016/j.bbrc.2022.02.019

Abstract

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.

Keywords: Acute pancreatitis; Inflammation; MCC950; Macrophage polarization; NLRP3 inflammasomes; Paeonol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetophenones
Acute Disease
Animals
Ceruletide / pharmacology
Inflammasomes* / metabolism
Macrophages / metabolism
Mice
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Pancreatitis* / chemically induced
Pancreatitis* / drug therapy
Reactive Oxygen Species / adverse effects

Substances

Acetophenones
Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse
Reactive Oxygen Species
paeonol
Ceruletide