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

Area of Science:

• Biochemistry
• Pharmacology
• Nephrology

Background:

• Diabetic nephropathy (DN) is a severe complication of type 2 diabetes (T2D), significantly increasing mortality risk.
• Effective treatments that manage T2D and prevent DN are crucial for patient outcomes.

Purpose of the Study:

• To investigate the therapeutic efficacy of Cuiyu tea polypeptides (TP) against DN.
• To elucidate the molecular mechanisms underlying TP's effects on DN.

Main Methods:

• Induction of diabetic nephropathy in mice using a high-fat diet and streptozotocin (HFD/STZ).
• Administration of TP (1000 mg/kg) for 5 weeks to assess its impact on glycemic control, insulin resistance, and kidney function markers.
• Analysis of molecular pathways, including polyol, PKCζ/JNK/NF-κB/TNF-α/iNOS, and AGEs/RAGE/TGF-β1, and podocin expression.

Main Results:

• TP significantly reduced fasting blood glucose by 52.04% and improved insulin resistance markers (HOMA-IR, HOMA-IS).
• TP treatment led to substantial reductions in urinary protein (34.51%), creatinine (42.24%), and urine nitrogen (80.30%), indicating improved glomerular filtration.
• TP modulated key signaling pathways, upregulated podocin expression, and decreased pro-inflammatory cytokine release.

Conclusions:

• Cuiyu tea polypeptides demonstrate significant therapeutic potential in mitigating diabetic nephropathy.
• TP exerts its protective effects by improving glycemic control, enhancing kidney function, and modulating specific molecular pathways involved in DN pathogenesis.