Arbutin attenuates LPS-induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway

Arbutin (Ar) has anti-oxidative and anti-inflammatory activities. However, the effects of Ar on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) are not clear. This study aimed to investigate the effects of Ar on LPS-induced AKI in rats. The possible data regarding the effects of Ar on AKI were collected by network pharmacology research. Histological changes in the kidney and the levels of blood urea nitrogen, serum creatinine, and kidney injury molecule 1 were measured to assess the effects of Ar on renal function in LPS-induced AKI. The levels of inflammatory were detected by live small-animal imaging, cytometric bead array and enzyme linked immunosorbent assay. The levels of reactive oxygen species and apoptosis of primary kidney cells were detected by flow cytometry. The oxidative stress-related markers were detected by the cuvette assay. The TLR4/NF-κB and PI3K/Akt/Nrf2 levels and apoptosis were detected by Western blot analysis. The effects of GDC-0068 (GDC, Akt inhibitor) on Ar interposed on LPS-induced NRK-52e cell apoptosis were investigated by flow cytometry. The data collected by network pharmacology suggested that Ar might inhibit AKI by exerting an anti-inflammatory effect and regulating the Akt signaling pathway. The experimental results showed that Ar markedly improved renal function, and attenuated inflammation and cell apoptosis via regulating PI3K/Akt/Nrf2 pathway following LPS challenge in vivo, which blocked by GDC effectively in vitro. In a word, this study demonstrated that Ar attenuated LPS-induced AKI by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway. This study was designed to examine the effects of arbutin (Ar) on lipopolysaccharide (LPS) induced AKI and the underlying mechanisms involved. The results showed that Ar has a protective effect on LPS-induced AKI in rats, which could ameliorate LPS induced AKI through inhibition of inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway, thus providing a molecular basis for a novel medical treatment of AKI. [Display omitted]