Nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a therapeutic target in many diseases， because it can induce antioxidant enzymes and other cytoprotective enzymes. Moreover， some Nrf2 activators have strong anti-inflammatory activities. Oxidative stress and inflammation are major components involved in the pathology of diabetic nephropathy. In the present study， we evaluated the Nrf2-dependent anti-oxidative and anti-inflammatory effects of digitoflavone in streptozotocin-induced diabetic nephropathy. The molecular mechanisms of digitoflavone were investigated in vitro using SV40-transformed mouse mesangial cells (SV40-Mes13). For the in vivo experiment， diabetes was induced in Nrf2+/+ ... More
Nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a therapeutic target in many diseases， because it can induce antioxidant enzymes and other cytoprotective enzymes. Moreover， some Nrf2 activators have strong anti-inflammatory activities. Oxidative stress and inflammation are major components involved in the pathology of diabetic nephropathy. In the present study， we evaluated the Nrf2-dependent anti-oxidative and anti-inflammatory effects of digitoflavone in streptozotocin-induced diabetic nephropathy. The molecular mechanisms of digitoflavone were investigated in vitro using SV40-transformed mouse mesangial cells (SV40-Mes13). For the in vivo experiment， diabetes was induced in Nrf2+/+ and Nrf2-/- mice by STZ injection， and digitoflavone was administered 2 weeks after the STZ injection. Digitoflavone induced Nrf2 activation and decreased oxidative damage， inflammation， TGF-β1 expression， extracellular matrix protein expression， and mesangial cell hyperplasia in SV40-Mes13 cells. Digitoflavone-treated Nrf2+/+ mice， but not Nrf2-/- mice， showed attenuated common metabolic disorder symptoms， improved renal performance， minimized pathological alterations， and decreased oxidative damage， inflammatory gene expression， inflammatory cell infiltration， TGF-β1 expression， and extracellular matrix protein expression. Our results show that the anti-oxidative and anti-inflammatory effects of digitoflavone are mediated by Nrf2 activation and that digitoflavone can be used therapeutically to improve metabolic disorders and relieve renal damage induced by diabetes.
