Sesamol Attenuates Renal Inflammation and Arrests Reactive-Oxygen-Species-Mediated IL-1β Secretion via the HO-1-Induced Inhibition of the IKKα/NFκB Pathway In Vivo and In Vitro

Author:

Tseng Kuo-FengORCID,Tsai Ping-HsuanORCID,Wang Jie-SianORCID,Chen Fang-Yu,Shen Ming-YiORCID

Abstract

Chronic nephritis leads to irreversible renal fibrosis, ultimately leading to chronic kidney disease (CKD) and death. Macrophage infiltration and interleukin 1β (IL-1β) upregulation are involved in inflammation-mediated renal fibrosis and CKD. Sesamol (SM), which is extracted from sesame seeds, has antioxidant and anti-inflammatory properties. We aimed to explore whether SM mitigates macrophage-mediated renal inflammation and its underlying mechanisms. ApoE–/– mice were subjected to 5/6 nephrectomy (5/6 Nx) with or without the oral gavage of SM for eight weeks. Blood and urine samples and all the kidney remnants were collected for analysis. Additionally, THP-1 cells were used to explore the mechanism through which SM attenuates renal inflammation. Compared with the sham group, the 5/6 Nx ApoE–/– mice exhibited a significant increase in the macrophage infiltration of the kidneys (nephritis), upregulation of IL-1β, generation of reactive oxygen species, reduced creatinine clearance, and renal fibrosis. However, the administration of SM significantly alleviated these effects. SM suppressed the H2O2-induced secretion of IL-1β from the THP-1 cells via the heme oxygenase-1-induced inhibition of the IKKα-NF-κB pathway. SM attenuated renal inflammation and arrested macrophage accumulation by inhibiting IKKα, revealing a novel mechanism of the therapeutic effects of SM on renal injury and offering a potential approach to CKD treatment.

Funder

Ministry of Science and Technology of Taiwan

China Medical University

China Medical University Hospital

Publisher

MDPI AG

Subject

Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology

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