Ellagic acid attenuates streptozocin induced diabetic nephropathy via the regulation of oxidative stress and inflammatory signaling

Diabetic nephropathy (DN) is the leading cause of chronic renal disease. Accumulating evidence suggested that oxidative stress and inflammatory processes are involved in the development of DN. In the present study, the DN model was established by injecting mice with STZ (180 mg*kg-1) intraperitoneally, and treated with EA (50, 100 and 150 mg*kg-1) and IRB (positive control) once daily by intragastric gavage. At the same time, rat kidney NRK-52E cells were cultured and incubated with EA and TAK-242 (inhibitor of TLR4) respectively before stimulating with LPS. The mental conditions, body weight, blood glucose, serum albumin (Alb), serum TNF-α, renal function, anti-oxidative enzymes, and protein expression of TLR4, IRAK4, TRAF6, IKKβ, NF-κb P65, HMGB1 in renal tissue were determined. Meanwhile, the proteins expression of TLR4, IRAK1 and NF-κBp65 in cells were further analyzed. The results showed that EA could improve the daily state and body weight; decrease the blood glucose, levels of TNF-α and serum creatinine; elevate the activities of antioxidant enzymes; ameliorate the renal pathology; inhibit the up regulation of expression of proteins TLR4, IRAK4, TRAF6, IKK-β, NF-κBp65 and HMGB1 in DN mice. These results suggested that EA ameliorated STZinduced oxidative renal injury by the inhibition of HMGB1-TLR4-NF-кB pathway.