Embelin attenuates lipopolysaccharide-induced acute kidney injury through the inhibition of M1 macrophage activation and NF-κB signaling in mice

Qiao Tang; Yun Tang; Qun Yang; Rong Chen; Hong Zhang; Haojun Luo; Qiong Xiao; Kaixiang Liu; Liming Huang; Jie Chen; Lin Wang; Xinrou Song; Sipei Chen; Guisen Li; Li Wang; Yi Li

doi:10.1016/j.heliyon.2023.e14006

Embelin attenuates lipopolysaccharide-induced acute kidney injury through the inhibition of M1 macrophage activation and NF-κB signaling in mice

Heliyon. 2023 Feb 26;9(3):e14006. doi: 10.1016/j.heliyon.2023.e14006. eCollection 2023 Mar.

Authors

Qiao Tang^{1

2}, Yun Tang^{2

3}, Qun Yang⁴, Rong Chen², Hong Zhang^{2

5}, Haojun Luo², Qiong Xiao², Kaixiang Liu², Liming Huang², Jie Chen⁶, Lin Wang⁷, Xinrou Song², Sipei Chen², Guisen Li^{2

3}, Li Wang^{2

3}, Yi Li^{2

3}

Affiliations

¹ North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
² 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.
³ Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, Sichuan, China.
⁴ 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.
⁵ Southwest Medical University, Luzhou, 646000, Sichuan, China.
⁶ 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.
⁷ 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.

Abstract

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-κB p65 at the ser536 site. Embelin inhibited the translocation of NF-κB p65 via phosphorylation at ser536 in LPS-induced AKI. It also reduced the secretion of IL-1β 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-κB p65 at ser536 in activated macrophages. This study preclinically suggests a therapeutic role of embelin in septic AKI.

Keywords: AKI, acute kidney injury; BMDMs, bone marrow-derived macrophages; BUN, blood urea nitrogen; DMEM, Dulbecco's modified eagle's medium; Embelin; FBS, fetal bovine serum; HE, hematoxylin & eosin; ICU, intensive care unit; IHC, immunohistochemistry; Inflammation; LPS, lipopolysaccharide; Macrophage; PAS, periodic-acid Schiff; Phosphorylated NF-κB p65 translocation; Scr, serum creatinine; Septic acute kidney injury; mIF, multiplex immunofluorescent.