PMID- 36934562 OWN - NLM STAT- MEDLINE DCOM- 20230425 LR - 20230425 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 118 DP - 2023 May TI - Oroxylin A relieves intrauterine adhesion in mice through inhibiting macrophage pyroptosis via SIRT3-SOD2-ROS pathway. PG - 110023 LID - S1567-5769(23)00344-2 [pii] LID - 10.1016/j.intimp.2023.110023 [doi] AB - Intrauterine adhesion (IUA) is manifested by endometrial fibrosis and inflammation, which seriously affects female reproductive health. Macrophages are mainly inflammatory cells and have been reported to participate in the fibrosis of IUA. Oroxylin A (OA), a kind of flavonoid compounds, was showed to possess the inhibitory effects on inflammation and fibrosis. However, the role of OA in IUA remains unclear. In the present study, we found that OA effectively alleviated the level of inflammation and uterine fibrosis in IUA mice. OA also decreased the macrophage pyroptosis which increased in uteri of IUA mice. Pyroptosis is a programmed cell death accompanied by an inflammatory response. Moreover, OA repressed the mediators of pyroptosis including the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), caspase-1 and Gasdermin D (GSDMD) and the release of IL-1beta, IL-18 and cleaved-caspase-1 in J774A.1 cells induced by LPS/ATP in vitro. Mechanistically, the alleviation of OA on uterine fibrosis is achieved by inhibiting macrophage pyroptosis via SIRT3-SOD2-ROS pathway. Our data indicate that OA may serve as an effective agent for the treatment of the endometrial fibrosis with IUA. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Yang, Jingjing AU - Yang J AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China. FAU - Li, Jingman AU - Li J AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China. FAU - Wang, Jiali AU - Wang J AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China. FAU - Wu, Jinjin AU - Wu J AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China. FAU - Yin, Lijie AU - Yin L AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China. FAU - Dou, Huan AU - Dou H AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: douhuan@nju.edu.cn. FAU - Hou, Yayi AU - Hou Y AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. Electronic address: yayihou@nju.edu.cn. LA - eng PT - Journal Article DEP - 20230317 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one) RN - EC 3.5.1.- (Sirtuin 3) RN - 0 (Flavonoids) RN - EC 3.4.22.36 (Caspase 1) RN - 0 (Sirt3 protein, mouse) SB - IM MH - Mice MH - Female MH - Animals MH - *Inflammasomes/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Reactive Oxygen Species/metabolism MH - *Sirtuin 3/metabolism MH - Pyroptosis MH - Macrophages/metabolism MH - Flavonoids/pharmacology/therapeutic use MH - Caspase 1/metabolism MH - Inflammation/metabolism MH - Fibrosis OTO - NOTNLM OT - Fibrosis OT - Intrauterine adhesion OT - Macrophage pyroptosis OT - Oroxylin A OT - SIRT3-SOD2-ROS pathway COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/20 06:00 MHDA- 2023/04/25 06:42 CRDT- 2023/03/19 19:04 PHST- 2022/11/01 00:00 [received] PHST- 2023/03/01 00:00 [revised] PHST- 2023/03/08 00:00 [accepted] PHST- 2023/04/25 06:42 [medline] PHST- 2023/03/20 06:00 [pubmed] PHST- 2023/03/19 19:04 [entrez] AID - S1567-5769(23)00344-2 [pii] AID - 10.1016/j.intimp.2023.110023 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 May;118:110023. doi: 10.1016/j.intimp.2023.110023. Epub 2023 Mar 17.