Drynachromoside A from Drynaria fortunei attenuates oxidative stress and fibrosis of diabetic nephropathy via activating Nrf2 in vitro and in vivo.

BACKGROUND: Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. It has shown that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) could attenuate DN. To identifiy novel Nrf2 activators targeting DN, we explored drynachromoside A (DCSA) from Drynaria fortunei in vitro and in vivo. METHODS: To determine the effects of DCSA, the proliferation of mesangial cells induced by high glucose was evaluated. And the renal function of db/db mice was evaluated. Meanwhile, oxidative stress and renal fibrosis in vitro and in vivo were further investigated. To elucidate the mechanism of DCSA, Nrf2 activation and its role in these effects were explored, and the interaction between Kelch-like ECH-associated protein 1 (Keap1) and DCSA was examined. RESULTS: DCSA inhibited the proliferation of mesangial cells resulting from high glucose and improved renal function in db/db mice. DCSA attenuated oxidative stress and fibrosis in vitro and in vivo, which was closely associated with Nrf2 activation in a Keap1-dependent manner. CONCLUSION: DCSA identified in Drynaria fortunei is a Keap1-dependent Nrf2 activator with the potential to attenuate DN. This investigation could provide novel insights into the discovery of Nrf2 activators and new therapeutic approaches for DN.