Fucoxanthin (Fx) has a unique chemical structure that confers its biological effects and shows potential health benefits. The main purpose of this study was to explore whether Fx could alleviate renal fibrosis in diabetic nephropathy (DN) by regulating p62/Keap1/Nrf2 signaling and improving mitochondrial damage. We found that Fx improved renal function, lipid metabolism and renal fibrosis in STZ-induced diabetic rats and alleviated fibrosis in HG-induced GMCs. And Fx regulated protein levels of p62, Keap1 and Nrf2 in kidneys of diabetic rats and HG-induced GMCs. Fx also upregulated protein levels of LC3 II/LC3 I, SOD1 and HO-1, reversed the over-production of mitochondrial superoxide, promoted the interaction between p62 and Keap1, improved mitochondrial morphology and mitochondrial membrane potential reduction and increased co-localization of p62 or Keap1 with mitochondria in HG-induced GMCs. Molecular docking study indicated the strong binding affinity between compound Fx and p62. Overall, Fx may be developed as a promising functional ingredient to alleviate DN.
