Abstract

Background Oxidative stress and inflammation play essential roles in the development and progression of diabetic nephropathy (DN). Baicalin (BAI), a natural flavonoid, has been showed to have a renoprotective effect in various renal diseases. However, its underlying mechanisms in DN remain unclear. In this study, we explored the potential effects and underlying mechanisms of BAI on DN using a spontaneous DN model.Methods The protective effects of BAI on DN have been evaluated by detecting DN-related biochemical indicators, kidney histopathology and cell apoptosis. After that, we examined the level of renal oxidative stress and inflammation to explain BAI’s renoprotective effects. Then, Nrf2 pathway was tested to clarify its antioxidant activity, and kidney transcriptomics was conducted to elucidate its anti-inflammatory activity. Finally, Western blot was applied for final mechanism verification.Results Our results found that BAI effectively ameliorated diabetic conditions, proteinuria, renal histopathological changes and cell apoptosis in DN. BAI significantly improved the kidney levels of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT), and reduced malondialdehyde (MDA) level. Meanwhile, the infiltration of inflammatory cells including T-lymphocytes, T-helper cells, neutrophils and macrophages, and the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6, MCP-1 and TNFα) were also obviously inhibited by BAI. Afterward, Western blot found that BAI significantly activated Nrf2 signaling and increased the expression of downstream antioxidant enzymes (HO-1, NQO-1). Kidney transcriptomics revealed that the inhibition of MAPK signaling pathway may contribute to BAI’s anti-inflammatory activity, which has also been verified in later experiment. BAI treatment did obviously inhibit the activation of canonical pro-inflammatory signaling pathwa