PMID- 36938407 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230321 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 3 DP - 2023 Mar TI - Embelin attenuates lipopolysaccharide-induced acute kidney injury through the inhibition of M1 macrophage activation and NF-kappaB signaling in mice. PG - e14006 LID - 10.1016/j.heliyon.2023.e14006 [doi] LID - e14006 AB - Septic acute kidney injury (AKI) is commonly associated with renal dysfunction and high mortality in patients. Owing to the rapid and violent occurrence of septic AKI with inflammation, there are no effective therapies to clinically treat it. Embelin, a natural product, has a potential regulatory role in immunocytes. However, the role and mechanism of embelin in septic AKI remains unknown. This study aimed to elucidate the role of embelin in macrophage regulation in lipopolysaccharide (LPS)-induced septic AKI. Embelin was intraperitoneally administered to mice after LPS injection. And bone marrow-derived macrophages (BMDMs) were subsequently isolated from the mice to explore the immunomodulatory role of embelin in macrophages. We found that embelin attenuated renal dysfunction and pathological renal damage in the LPS-induced sepsis mouse model. Molecular docking predicted that embelin could bind to phosphorylated NF-kappaB p65 at the ser536 site. Embelin inhibited the translocation of NF-kappaB p65 via phosphorylation at ser536 in LPS-induced AKI. It also reduced the secretion of IL-1beta and IL-6 and increased the secretion of IL-10 and Arg-1 of BMDMs and mice after LPS stimulation, indicating that embelin suppressed macrophage M1 activation in LPS-induced AKI. Therefore, embelin attenuated LPS-induced septic AKI by suppressing NF-kappaB p65 at ser536 in activated macrophages. This study preclinically suggests a therapeutic role of embelin in septic AKI. CI - (c) 2023 The Authors. FAU - Tang, Qiao AU - Tang Q AD - North Sichuan Medical College, Nanchong, 637000, Sichuan, China. AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Tang, Yun AU - Tang Y AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. AD - Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, Sichuan, China. FAU - Yang, Qun AU - Yang Q AD - Department of Pathology, School of Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Chen, Rong AU - Chen R AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Zhang, Hong AU - Zhang H AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. AD - Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Luo, Haojun AU - Luo H AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Xiao, Qiong AU - Xiao Q AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Liu, Kaixiang AU - Liu K AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Huang, Liming AU - Huang L AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Chen, Jie AU - Chen J AD - Central Laboratory, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Wang, Lin AU - Wang L AD - Institute of Laboratory Animal Sciences, School of Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Song, Xinrou AU - Song X AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Chen, Sipei AU - Chen S AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. FAU - Li, Guisen AU - Li G AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. AD - Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, Sichuan, China. FAU - Wang, Li AU - Wang L AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. AD - Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, Sichuan, China. FAU - Li, Yi AU - Li Y AD - Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China. AD - Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, Sichuan, China. LA - eng PT - Journal Article DEP - 20230226 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC10018479 OTO - NOTNLM OT - AKI, acute kidney injury OT - BMDMs, bone marrow-derived macrophages OT - BUN, blood urea nitrogen OT - DMEM, Dulbecco's modified eagle's medium OT - Embelin OT - FBS, fetal bovine serum OT - HE, hematoxylin & eosin OT - ICU, intensive care unit OT - IHC, immunohistochemistry OT - Inflammation OT - LPS, lipopolysaccharide OT - Macrophage OT - PAS, periodic-acid Schiff OT - Phosphorylated NF-kappaB p65 translocation OT - Scr, serum creatinine OT - Septic acute kidney injury OT - mIF, multiplex immunofluorescent COIS- The authors declare no competing interests. EDAT- 2023/03/21 06:00 MHDA- 2023/03/21 06:01 PMCR- 2023/02/26 CRDT- 2023/03/20 04:18 PHST- 2022/07/26 00:00 [received] PHST- 2023/01/27 00:00 [revised] PHST- 2023/02/17 00:00 [accepted] PHST- 2023/03/20 04:18 [entrez] PHST- 2023/03/21 06:00 [pubmed] PHST- 2023/03/21 06:01 [medline] PHST- 2023/02/26 00:00 [pmc-release] AID - S2405-8440(23)01213-6 [pii] AID - e14006 [pii] AID - 10.1016/j.heliyon.2023.e14006 [doi] PST - epublish SO - Heliyon. 2023 Feb 26;9(3):e14006. doi: 10.1016/j.heliyon.2023.e14006. eCollection 2023 Mar.