Hesperetin and Isoliquiritigenin Attenuate the Progression of Diabetic Nephropathy via Inhibition of NF-κB/NLRP3 Pathways in Type 2 Diabetic Rats.

Glucose toxicity associated with oxidant and inflammatory triggers causes diabetic nephropathy (DN), thus necessitating the investigation of potential therapeutic interventions. This study investigated the nephroprotective activities of hesperetin (HSP) and isoliquiritigenin (ISL) in diabetic rats. Type 2 diabetes (T2D) was generated in Wistar rats by feeding them a high-fat diet (HFD, ) and injecting intraperitoneally with a single dose of streptozotocin (35 mg/kg). T2D rats were then administered orally HSP (50 and 100 mg/kg), ISL (10 and 20 mg/kg), and metformin (180 mg/kg) for 4 weeks along with the continuous feeding of HFD. The study assessed various renal function parameters, including kidney index, kidney inflammatory biomarkers, kidney oxidative stress biomarkers, fasting blood glucose, serum insulin, serum lipids, blood urea nitrogen, serum creatinine, urine protein, creatinine clearance, protein/creatinine ratio, renal histopathology, and relative gene expressions of kidney NLRP3 and NF-κB proteins, comparing these parameters with normal and diabetic control groups. The findings indicated that HSP and ISL attenuated the pathological progression of DN, as demonstrated through the normalization of various biochemical and gene expression biomarkers, indicating a marked anti-inflammatory and antioxidant effect, improved kidney histology, and mitigated renal dysfunction. These findings suggest that HSP and ISL exhibit nephroprotective effects via mechanisms including inhibition of NLRP3 and NF-κB activation, decrease in oxidative stress, and improvement of the blood glucose status of T2D rats.