Association analysis-based screening strategy for quality markers of Tengdan Capsule in the treatment of hypertensive renal disease

Hypertensive Renal Disease (HRD) is a chronic and progressive condition driven by sustained high blood pressure, which leads to renal fibrosis and, eventually, end-stage kidney failure. Tengdan Capsule (TDC), a traditional Chinese medicinal formulation, has shown therapeutic potential for managing HRD. However, the specific quality markers (Q-markers) responsible for its efficacy and the underlying molecular mechanisms remain insufficiently understood. This study aimed to identify candidate Q-markers of TDC and elucidate the molecular pathways through which it exerts its renoprotective effects, using an integrative association analysis-based approach. Methods: The chemical composition of TDC and its potential Q-markers were systematically characterized through in vitro and in vivo profiling using HPLC-Q-Exactive-MS and chromatographic fingerprinting. Transcriptomic analysis was conducted on angiotensin II-stimulated HEK293T cells to identify differentially expressed genes (DEGs) responsive to candidate Q-markers. Mendelian randomization (MR) analysis based on genome-wide association study (GWAS) data was employed to validate causal genes linked to HRD. Furthermore, untargeted metabolomics was performed to explore metabolic changes associated with transcriptomic targets.