Exploring the kidney-protective potential of traditional Zhuang medicine 'Yingbupu': Insights from serum metabolomics, network pharmacology, and experimental validation.

Abstract

ETHNOBOTANICAL RELEVANCE: Proteinuria is a key indicator and therapeutic difficulty in the progression of kidney diseases. Yingbupu (YBP), an ethnic medicine, has demonstrated significant proteinuria-lowering effects in folk applications, but its exact nephroprotective effects and molecular mechanisms are still unclear. AIM OF STUDY: To investigate the nephroprotective effect of YBP and its mechanism of action. METHOD AND RESULTS: UPLC-Q-Orbitrap HRMS technology was used to analyze the absorbed constituents of YBP, and integrated methods of network pharmacology, molecular docking, and adriamycin renal injury model rat experiments (observation of general indexes, urinary proteins, ultrastructure of renal tissues, immunohistochemistry, WB, and PCR) were used to evaluate the renoprotective effects and mechanisms of action of YBP. Twenty-four absorbed constituents were identified in YBP, and 136 key targets were screened. Enrichment analysis suggested that the Wnt/β-catenin signaling pathway might play a central role. Animal experiments confirmed that YBP could significantly improve renal injury and reduce urinary protein level, inhibit the reduction of β-catenin nuclear translocation, and significantly down-regulate the expression of target genes such as Cyclin D1 and Axin-2. CONCLUSION: The renoprotective effect of YBP can be attributed to its ability to effectively reverse the abnormal activation of Wnt/β-catenin pathway.