Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation

• Published in: Phytotherapy research Vol. 34; no. 1; pp. 139 - 152
• Main Authors: Tan, Rui‐Zhi, Wang, Chen, Deng, Chong, Zhong, Xia, Yan, Ying, Luo, Yi, Lan, Hui‐Yao, He, Tao, Wang, Li
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2020
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; AKI; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Bone marrow; Chemotherapy; Cisplatin; Cisplatin - adverse effects; Creatinine; Disease Models, Animal; Flavonoids; Humans; Inflammation; Inflammation - drug therapy; Injuries; Kidney diseases; Kidneys; Lipopolysaccharides; macrophage; Macrophages; Male; Mice; Mincle; Quercetin; Quercetin - pharmacology; Signaling; Syk protein; Tumor necrosis factor; macrophage; quercetin; Mincle; inflammation; AKI
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6507

Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF‐κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL‐1β, IL‐6, and TNF‐α in LPS‐induced bone marrow‐derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF‐κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL‐1β, IL‐6, and TNF‐α in cisplatin‐induced AKI model. Furthermore, quercetin down‐regulated protein levels of Mincle, phosphorylated Syk and NF‐κB in kidney macrophages of AKI, as well as inhibited M1, up‐regulated M2 macrophage activity. Notably, the down‐regulation of LPS‐induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI‐induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.