Abstract: Objective: To determine the protective effect and underlying mechanism of melanin extracted from cuttlefish ink sacs on streptozocin-induced diabetic nephropathy in mice. Methods: Diabetic nephropathy was induced in mice by intraperitoneal injection of streptozocin (STZ). The experimental mice were randomly divided into 6 groups: normal control, model control, positive control, low-dose (120 mg/kg), medium-dose group (240 mg/kg), and high-dose melanin (480 mg/kg) groups. After four weeks of oral administration, kidney index, kidney function and antioxidant enzymes activities were measured, and the kidneys were histologically examined. The mRNA expression of renal fibrogenic cytokines was detected by real time polymerase chain reaction (RT-PCR). Results: Compared with the model control group, the medium- and highdosage groups showed significantly enhanced kidney function (P < 0.01), increased antioxidant enzyme activities (P < 0.05 or P < 0.01), reduced mRNA expression of transforming growth factor-β1 (TGF-β1) and its receptors, and increased mRNA expression of peroxisome proliferators-activated receptor-g (PPAR-g) (P < 0.01). Moreover, high-dosage melanin reduced extracellular matrix accumulation in the basal and mesangial regions of renal tubular cells and decreased tubulointerstitial fibrosis, while no significant differences were observed for the low-medium melanin group. Conclusion: Melanin from cuttlefish ink can relieve diabetic renal inflammation, likely by enhancing renal antioxidant capacity and inhibiting the overexpression of renal fibrogenic cytokines.

Key words: melanin extracted from cuttlefish ink sacs, diabetic nephropathy, cytokines