Cortex phellodendri Exerts Its Nephroprotective Effect via the Inhibition of the AGEs‐RAGE Pathway

Diabetic nephropathy (DN) is a leading microvascular complication of diabetes, with limited effective treatments. Cortex phellodendri (CP), a traditional Chinese medicine known for its diverse chemical constituents, exhibits various pharmacological properties, including antibacterial and hypoglycemic effects. However, the precise mechanisms by which CP addresses DN remain unclear. This study explores the nephroprotective effects of CP in a type 2 diabetic mouse model induced by a high-fat diet and streptozotocin. After 14 weeks of drug intervention, we assessed serum biomarkers (fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, and serum creatinine) and urinary biomarkers (urea nitrogen, urinary creatinine, urinary albumin-to-creatinine ratio, and 24-h urinary protein) in DN mice. Pharmacological results indicate that CP possesses the capacity to regulate disorders of glucose and lipid metabolism and improve renal dysfunction. We utilized ultra-performance liquid chromatography-high-resolution tandem mass spectrometry to characterize the chemical constituents of CP and conducted a network pharmacology analysis on its plasma-absorbed components. Histopathological examination of kidney sections was performed using hematoxylin-eosin, Periodic acid-schiff, and Masson staining. Additionally, Western blotting was used to detect proteins related to the AGEs/RAGE axis. CP alleviates DN by inhibiting the AGEs/RAGE pathway. This research seeks to provide a scientific foundation for the clinical application of CP in managing diabetic kidney disease.