The chemical-pharmacological continuum of Yucan formula: Integrated component-tissue exposure correlation informs...

This study focuses on uncovering the material basis and therapeutic mechanisms of the Yucan Formula (YCF) in the treatment of diabetic kidney disease (DKD). Utilizing a combination of UHPLC-Q-Exactive Orbitrap HRMS and AB Sciex Triple Quad™ 4500 LC-MS, a comprehensive qualitative and quantitative analysis of YCF's chemical constituents was performed. A total of 166 compounds were identified, primarily flavonoids (57), terpenoids (32), organic acids (25), and phenylpropanoids (15), with fragmentation patterns established for the major classes and tissue distribution characteristics investigated. In vivo distribution studies identified prototype compounds present in both blood and kidney, and through peak area screening and methodological validation, eight key compounds (Senkyunolide H, Senkyunolide I, Nobiletin, 3-n-Butylphthalide, Senkyunolide A, Methylnissolin, Ferulic Acid and p-Coumaric acid) were selected for pharmacokinetic analysis. These compounds demonstrated rapid absorption, prolonged retention time, and strong pharmacological potential. By integrating data from TCMSP, SwissTargetPrediction, and other databases, a compound-target-disease network was constructed, revealing through GO and KEGG enrichment analyses that YCF primarily exerts its effects via pathways such as AGE-RAGE, PI3K-AKT, and MAPK, thereby regulating oxidative stress, inflammation, and fibrosis. These findings highlight the multi-component, multi-target, and multi-pathway synergistic nature of YCF in the treatment of DKD. Collectively, this study elucidates the in vivo behavior and active constituents of YCF while constructing a scientific mechanism-based network, offering a systematic pharmacological model for exploring traditional Chinese medicine formulas in the management of complex diseases.