Yipishen Xiezhuo Jiedu Decoction in Ameliorating Kidney Damage Through miR-223/NLRP3/ Caspase-1 Pathway

Introduction: Hyperuricemia Nephropathy (HN) is an emerging metabolic disorder that predisposes individuals to Chronic Kidney Disease (CKD), yet effective treatments remain limited. Inflammation plays a pivotal role in HN-induced kidney injury, with the NLRP3 inflammasome serving as a central mediator of this process. This study investigates the therapeutic effects of Yipishen Xiezhuo Jiedu Decoction (YPSXZJDD), a traditional Chinese medicine, on HNinduced kidney injury through the miR-223/NLRP3/Caspase-1 pathway. Materials and Methods: The key active components of YPSXZJDD were screened using UHPLC- Q Exactive Orbitrap-MS, and a Protein-Protein Interaction (PPI) network diagram was constructed to explore potential mechanisms of action. The identified components were then utilized to intervene in both cellular and animal models of hyperuricemic nephropathy, evaluating their therapeutic effects and underlying mechanisms. Results: Catalpol and Tanshinone IIA were identified as the key active components of YPSXZJDD. These compounds significantly mitigated renal epithelial cell apoptosis and inflammation by upregulating miR-223, which in turn inhibited the NLRP3/Caspase-1 pathway. The upregulation of miR-223 led to a marked reduction in NLRP3 activity and inflammatory responses, thereby alleviating HN-induced kidney damage. Discussion: The findings of this study underscore the critical role of miR-223 in regulating the NLRP3 inflammasome and highlight its potential as a therapeutic target for HN. The inhibition of the NLRP3/Caspase-1 pathway by miR-223 significantly reduces inflammation and renal injury, demonstrating the therapeutic efficacy of YPSXZJDD. These results offer a novel perspective on the application of traditional Chinese medicine in treating HN, highlighting the importance of miR-223 in regulating inflammation. Conclusion: This study demonstrates that YPSXZJDD alleviates HN-induced kidney injury by upregulating miR-223 and inhibiting the NLRP3/Caspase-1 pathway. The therapeutic potential of YPSXZJDD is supported by its ability to mitigate inflammation and renal damage, offering a promising approach for HN treatment. Further research into the broader role of miR-223 in kidney disease and related conditions is warranted to expand the understanding of its therapeutic applications.