Tiliroside from Potentilla chinensis attenuates oxidative stress and accumulation of ECM in mesangial cells under high glucose via activating Nrf2

Diabetic nephropathy (DN) is one of the severe microvascular complications of diabetes mellitus and it was proved activation of nuclear factor erythroid 2-related factor 2 (Nrf2) could attenuate DN. To find Nrf2 acti-vators, we explored tiliroside identified from Potentilla chinensis using mesangial cells under high glucose. The results showed tiliroside ameliorated oxidative stress via reducing the overproduction of ROS and MDA as well as enhancing the decreased activity of superoxide dismutase, catalase, and glutathione peroxidase. Meanwhile, tiliroside attenuated the accumulation of extracellular matrix (ECM) including collagen IV, laminin and fibro-nectin resulting from high glucose through down-regulating transforming growth factor beta 1 and connective tissue growth factor. Further investigations revealed activation of Nrf2 by tiliroside was involved in the effects against oxidative stress and accumulation of ECM, and the activation of Nrf2 was dependent on the interaction between Kelch-like ECH-associated protein-1 (Keap1) and tiliroside to disrupt the Keap1-Nrf2 complex.