Quercetin Nanoparticle Ameliorates Lipopolysaccharide-Triggered Renal Inflammatory Impairment by Regulation of Sirt1/NF-KB Pathway

As a conventional complication of sepsis, acute kidney injury (AKI) is characterized by high incidence and mortality. Effective management methods are still lacking. Quercetin belongs to a kind of Flavonoids that exerts many functions, for example anti-inflammation and anti-fibrosis. However, its function in sepsis AKI is uncertain. Our study therefore set out to assess the function of quercetin in AKI mice model induced by lipopolysaccharide (LPS) and human proximal tubular cells (HK-2), including the potential mechanisms. Quercetin was loaded onto a biodegradable polymer carrier (nanoparticle) to enhance its bioavailability. The data showed that quercetin administration strikingly improved renal dysfunction and ameliorated tubular injury caused by LPS in mice. In mice model and in cultured cells, quercetin pretreatment obviously restrained LPS-triggered cell Apoptosis and inflammation, including generation of various cytokines. Moreover, the results from mice model and cell model showed that quercetin could diminish IκBα and p65 phosphorylation after LPS treatment. The most significant observation of this study was that quercetin elevated the expression of SIRT1. Transfection of SIRT1 specific shRNA mitigated the suppression of quercetin on cell Apoptosis, inflammation and of NF-κB activation triggered by LPS. Therefore, these sequels indicate that quercetin protects against sepsis-associated AKI by upregulation SIRT1 expression through quenching NF-κB activation and may be an encouraging therapeutic agent for patients with sepsis-associated AKI.