Tea Polypeptide Ameliorates Diabetic Nephropathy through RAGE and NF-κB Signaling Pathway in Type 2 Diabetes Mice

Diabetic nephropathy (DN) is a major complication of type 2 diabetes (T2D), which is a key determinant of mortality in diabetic patients. Developing new therapeutic drugs which can not only control T2D but also prevent the development of DN is of great significance. We studied the therapeutic potential of Cuiyu tea polypeptides (TP), natural bioactive peptides isolated from a type of green tea, against DN and its underlying molecular mechanisms. TP (1000 mg/kg bw/day, p.o.) administration for 5 weeks significantly reduced the fasting blood glucose by 52.04 ± 9.23% in the high fat diet/streptozocin (HFD/STZ)-induced (30 mg/kg bw) diabetic mice. Compared to the model group, the serum insulin level of the TP group was decreased by 25.54 ± 6.06%, while at the same time, the HOMA-IR, HOMA-IS, and lipid levels showed different degrees of recovery (p < 0.05). Moreover, in TP group mice the total urinary protein, creatinine, and urine nitrogen, all which can reflect the damage degree of the glomerular filtration function to a certain extent, dramatically declined by 34.51 ± 2.65%, 42.24 ± 15.24%, and 80.30 ± 6.01% compared to the model group, respectively. Mechanistically, TP stimulated the polyol PKCζ/JNK/NF-κB/TNF-α/iNOS and AGEs/RAGE/TGF-β1 pathways, upregulated the expression of podocin in the glomeruli, and decreased the release of pro-inflammatory cytokines. These results strongly indicate the therapeutic potential of TP against DN