Qing-Re-Xiao-Zheng-yi-qi formula protects kidney function by stabilizing cell waste compartments and reducing inflammation-related cell death in diabetic kidney disease
QRXZYQF may protect podocytes in models by stabilizing lysosomes and reducing NLRP3-mediated .
Evidence
This preclinical study used STZ-induced male C57BL/6J diabetic mice treated for 12 weeks plus cultured podocytes to assess renal injury, markers, and Cathepsin B leakage.
Caveat
The evidence is mechanistic and preclinical, so the abstract does not establish clinical benefit, dosing, or safety in DKD patients.
Simplified
BACKGROUND: Qing-Re-Xiao-Zheng-Yi-Qi formula (QRXZYQF), based on the "Shen-Luo-Zheng-Jia" principles of traditional Chinese medicine, has been reported to reduce 24-hour urinary total protein in (DKD) patients, slow disease progression, and improve podocyte injury. This study aims to explore the mechanisms of QRXZYQF in improving podocyte injury.
METHODS: Diabetes was induced in male C57BL/6J mice by intraperitoneal injection of streptozotocin (STZ). After 12 weeks of QRXZYQF, blood glucose, blood urea nitrogen, serum creatinine, microalbumin, and the urinary albumin-to-creatinine ratio (UACR) were monitored. Renal pathological changes were evaluated using hematoxylin and eosin (H&E), Masson, and periodic acid-Schiff (PAS) staining. RNA sequencing (RNA-Seq) was performed to identify differences in renal mRNA expression and enrichment pathways. The involvement of autophagy-lysosomal and NOD-like receptor pathways was examined by western blotting and immunofluorescence in renal tissues and cultured podocytes.
RESULTS: Following 12 weeks of QRXZYQF, renal function improved and ECM accumulation and glomerulosclerosis were markedly reduced. Subsequently, RNA-Seq analysis showed that the autophagy-lysosomal and NOD-like receptor signaling pathways were the potential pathways involved in the mechanism of QRXZYQF. Moreover, QRXZYQF reduced the levels of NLRP3, apoptosis-associated speck-like protein (ASC), as well as Caspase-1 in vitro. Furthermore, we performed interventions using the lysosomal membrane-permeabilizing agent (L-leucyl-L-leucine-O-methylester) and found that QRXZYQF inhibits NLRP3 overexpression by protecting lysosomal membranes and preventing the leakage of Cathepsin B (CB) into the cytoplasm.
CONCLUSIONS: QRXZYQF inhibits NLRP3-mediated podocyte by stabilizing lysosomal membranes, providing insights into its protective mechanism and potential therapeutic targets for DKD.
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