Pueraria lobata extract mitigates diabetic nephropathy via NLRP3 inflammasome and Caspase-1 regulation.

To elucidate novel mechanisms underlying puerariae lobatae extract (EPL) therapeutic efficacy against diabetic nephropathy, with a focus on NLRP3 inflammasome regulation in streptozotocin (STZ)-induced renal pathology. 60 Wistar rats were randomly divided into five groups: a normal control (NC) group, a model (Model) group, an EPL (EPL) group, an NLRP3 activator group (NLRP3), and an NLRP3 activator + EPL group (NLRP3 + EPL), with 12 rats in each group. Diabetic kidney injury was induced in rats by intraperitoneal injection of streptozotocin (STZ). ELISA was used to measure serum creatinine (Scr), blood urea nitrogen (BUN), serum uric acid (SUA), 24-hour urinary albumin (UAlb), malondialdehyde (MDA) in renal tissue, superoxide dismutase (SOD), interleukin-1β (IL-1β), and IL-18. Histopathological changes in renal tissue were observed by hematoxylin and eosin (HE) staining. The content of reactive oxygen species (ROS) in renal tissue was detected by chemiluminescence. qRT-PCR was employed to detect the mRNA expression of NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in renal tissue. Western blot was used to assess the protein expression of NLRP3, ASC, and cysteine aspartic acid protease 1(caspase-1) in renal tissue. EPL intervention demonstrated: Significant body weight recovery (143.62 ± 6.18 g vs. DN 110.53 ± 5.69 g, P < 0.05); Renal functional restoration: 34.8% reduction in Scr (15.96 ± 2.31 vs. 35.19 ± 5.27 µmol/L), 49.7% decrease in BUN (9.16 ± 0.35 vs. 18.21 ± 0.85 mmol/L); Oxidative homeostasis improvement: 35.5% MDA reduction (2.38 ± 0.31 vs. 3.69 ± 0.42 nmol/mg), 56.8% ROS suppression (25.52 × 10⁴ vs. 59.08 × 10⁴/mg); Inflammasome downregulation: 62.3% decrease in NLRP3 mRNA, 58.1% ASC protein reduction, and 47.6% Caspase-1 activation inhibition. This study establishes that EPL ameliorates diabetic renal injury by suppressing NLRP3 inflammasome activation and Caspase-1-mediated signaling, providing mechanistic validation for EPL's therapeutic potential in metabolic nephropathy management.