Ellagic acid protects against diabetic nephropathy in rats by regulating the transcription and activity of Nrf2

Abstract This study examined if the protective effect of Ellagic acid (EA) against streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats involves activation of Nrf2. Diabetes mellitus was induced by a single i.p dose of STZ (65 mg/kg). The Rats were divided into 5 groups (n = 12/each) and treated for 8 weeks as control, control + EA (100 mg/kg), STZ, STZ + EA (100 mg/kg), and STZ + EA + trigonelline (Nrf2 inhibitor/0.2 mg/kg). EA prevented renal damage, oxidative stress, inflammation, and apoptosis. These effects were associated with reduced activity of NF-κB, upregulated GSH, γ-GCL, and SOD, and increased the nuclear translocation of Nrf2. Besides, EA suppressed the cytoplasmic expression of keap1 and its interaction with Nrf2, increased the phosphorylation of Akt and GS3Kβ, and reduced the phosphorylation and nuclear accumulation of Fyn. All these alterations were abolished by trigonelline. In conclusion, EA ameliorates DN in rats by antioxidant and anti-inflammatory potentials.