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.