PMID- 36229953 OWN - NLM STAT- MEDLINE DCOM- 20230213 LR - 20230213 IS - 1099-0461 (Electronic) IS - 1095-6670 (Linking) VI - 37 IP - 2 DP - 2023 Feb TI - Proanthocyanidins suppress NLRP3 inflammasome and M1 macrophage polarization to alleviate severe acute pancreatitis in mice. PG - e23242 LID - 10.1002/jbt.23242 [doi] AB - The role of reactive oxygen species (ROS) is crucial for the pathogenesis of acute pancreatitis (AP). Proanthocyanidins (PAs) have been confirmed to exert antioxidant activity. Our study aimed to determine whether PAs alleviated SAP via reducing ROS, suppressing NLRP3 inflammasome, and inhibiting M1 macrophage polarization. Our study investigated the protective effects of PAs on pancreatic histopathological injury using SAP mice. The effects of PAs on macrophages were investigated in inflammatory RAW 264.7 cells or mouse bone marrow-derived macrophages (BMDMs) induced by lipopolysaccharide (LPS). Immunofluorescence staining and/or western blot assay were employed to evaluate NLRP3 inflammasome in macrophages and pancreatic tissue. Cell counting kit-8 (CCK-8) was used to access effects of PAs on cell viability and cytometry flow was used to determine the effects of the PAs on the ROS levels of the RAW 264.7 cells. Then, we evaluated M1 macrophage polarization using flow cytometry or real-time quantitative polymerase chain reaction (RT-qPCR). PAs administration alleviated pancreatic inflammation in SAP mice. The PAs depressed NLRP3 inflammasome and inhibited M1 macrophage polarization in pancreatic tissue. We also found that the PAs showed no cellular toxicity but decreased ROS levels in RAW 264.7 cells, downregulated the NLRP3 inflammasome in the macrophages, and inhibited cell M1 macrophage polarization. Our study indicates the anti-inflammatory properties of the PAs on SAP mice by decreasing ROS levels, suppressing NLRP3 inflammasome, and M1 macrophage polarization. CI - (c) 2022 Wiley Periodicals LLC. FAU - Sheng, Li-Ping AU - Sheng LP AUID- ORCID: 0000-0002-6490-3845 AD - Department of Gastroenterology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Han, Chao-Qun AU - Han CQ AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Ling, Xin AU - Ling X AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Guo, Xian-Wen AU - Guo XW AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Lin, Rong AU - Lin R AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Ding, Zhen AU - Ding Z AD - Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. AD - Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. LA - eng GR - 81770637/National Natural Science Foundation of China/ GR - 82070667/National Natural Science Foundation of China/ PT - Journal Article DEP - 20221013 PL - United States TA - J Biochem Mol Toxicol JT - Journal of biochemical and molecular toxicology JID - 9717231 RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Proanthocyanidins) RN - 0 (Reactive Oxygen Species) RN - 0 (Nlrp3 protein, mouse) SB - IM MH - Mice MH - Animals MH - Inflammasomes MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - *Proanthocyanidins/pharmacology MH - *Pancreatitis/chemically induced/drug therapy MH - Reactive Oxygen Species MH - Acute Disease MH - Macrophages OTO - NOTNLM OT - M1 macrophage polarization OT - NLRP3 inflammasome OT - proanthocyanidins OT - reactive oxygen species OT - severe acute pancreatitis EDAT- 2022/10/15 06:00 MHDA- 2023/02/14 06:00 CRDT- 2022/10/14 01:23 PHST- 2022/07/28 00:00 [revised] PHST- 2021/12/19 00:00 [received] PHST- 2022/09/22 00:00 [accepted] PHST- 2022/10/15 06:00 [pubmed] PHST- 2023/02/14 06:00 [medline] PHST- 2022/10/14 01:23 [entrez] AID - 10.1002/jbt.23242 [doi] PST - ppublish SO - J Biochem Mol Toxicol. 2023 Feb;37(2):e23242. doi: 10.1002/jbt.23242. Epub 2022 Oct 13.