Simiao pills alleviates renal injury associated with hyperuricemia: A multi-omics analysis

Ethnopharmacological relevance: Simiao Pills, a classical traditional Chinese medicine prescription recorded in Cheng Fang Bian Du, has been traditionally used to treat hyperuricemia due to its heat-clearing and diuretic properties. Studies have shown that Simiao Pills effectively reduce uric acid levels. However, further research is needed to elucidate the precise composition of Simiao Pills for treating hyperuricemia and their potential pharmacological mechanism. Aim of the study: This study aimed to investigate the therapeutic effects of Simiao Pills on hyperuricemia, with a particular focus on evaluating their protective role against hyperuricemia-induced renal injury and elucidating the underlying mechanism of action. Materials and methods: UPLC-MS/MS was used to identify the components of Simiao Pills. The hyperuricemia model mice were established by intraperitoneal injecting potassium oxonate (PO) and oral administrating hypoxanthine (HX). Network pharmacology, transcriptome, and metabolomics analyses were integrated to explore the mechanism of Simiao Pills in reducing uric acid and protecting the kidney. Mechanistic and functional studies were conducted to validate the potential mechanisms. Results: Simiao Pills were found to contain 12 characteristic components. Treatment with Simiao Pills significantly reduced serum uric acid levels and ameliorated hyperuricemia-induced renal injury. Simiao Pills inhibited the enzymatic activities of XOD and XDH, and regulated the uric acid transporters in the kidney and ileum. Transcriptome and network pharmacology analyses highlighted quercetin, berberine, kaempferol, and baicalein as the principal active components of Simiao Pills acting on the kidney during hyperuricemia treatment, primarily impacting fibrosis, apoptosis, and inflammation-related signaling pathways. Metabolomic analysis unveiled 21 differential metabolites and 5 metabolic pathways associated with Simiao Pills against renal injury associated with hyperuricemia. Further experimental results validated that Simiao Pills reduced renal fibrosis, apoptotic renal cells, serum inflammation levels, and inhibited the NF-κB/NLRP3/IL-1β signaling pathway. Conclusion: This study demonstrated that Simiao Pills significantly reduced serum uric acid levels and improved renal injury by regulating inflammation, apoptosis, and renal fibrosis. These findings have provided a robust scientific pharmacological basis for the use of Simiao Pills in treating hyperuricemia patients.