Aucubin alleviates diabetic nephropathy by inhibiting NF-κB activation and inducing SIRT1/SIRT3-FOXO3a signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Oxidative stress and inflammation are two important pathological mechanisms in diabetic nephropathy (DN). Aucubin (AU), a natural iridoid glucoside, possessing remarkable anti-inflammatory and anti-oxidation activity, has been used to treat diabetic complications. However, underlying mechanism of protective action in DN remains unclear. In the present study, AU significantly alleviated albuminuria, glomerular extracellular matrix expansion, renal fibrosis, and inflammation caused by diabetes after ten weeks of treatment. Moreover, AU significantly inhibited oxidative stress markers in kidney tissue. In addition, we demonstrated that AU promoted endogenous antioxidant defenses by triggering Nrf2 and FOXO3a nuclear translocation, respectively, and up-regulation of antioxidant genes, including NQO1, HO-1, Mn-SOD, and CAT. These effects may be, in part, mediated by inducing SIRT1 and SIRT3 activities. Furthermore, AU also attenuated pro-inflammatory cytokines in renal tissue by inhibiting the NF-κB signaling pathway. Taken together, our results suggested that AU is a potential natural agent for the prevention of diabetes-induced DN.