ArticleAnnals of medicine2025
Qing-Re-Xiao-Zheng-yi-qi formula protects renal function by stabilizing lysosomal membranes and inhibiting NLRP3-inflammasome-mediated pyroptosis in diabetic kidney disease.
Article in Annals of medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundQing-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 diabetic kidney disease (DKD) patients, slow disease progression, and improve podocyte injury. This study aims to explore the mechanisms of QRXZYQF in improving podocyte injury.
methodsDiabetes 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.
resultsFollowing 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.
conclusionsQRXZYQF inhibits NLRP3-mediated podocyte pyroptosis by stabilizing lysosomal membranes, providing insights into its protective mechanism and potential therapeutic targets for DKD.
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