Abstract
Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus. Oxidative stress and fibrosis largely contribute to the progression of DN. Recently, Nrf2 was found to be a potential target preventing DN. In the discovery of novel Nrf2 activators for the treatment of DN, we have evaluated coumarin derivatives from Wikstroemi indiaca. Molecular docking results have shown compound 4 could bind to Keap1 and activate Nrf2 significantly. Cell-based assays have revealed compound 4 activated Nrf2 and attenuated oxidative stress and fibrosis induced by high glucose in mesangial cells. Meanwhile, it was validated that disruption of the interaction between Keap1 and Nrf2 was involved in the activation of Nrf2 by compound 4 in mesangial cells under high glucose.
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