Elucidation of the Material Basis of Yiqi Qingjie Formula Against IgA Nephropathy Using UHPLC-Q-Orbitrap HRMS Integrated with Network Pharmacology

This study employs UHPLC-Q-Orbitrap HRMS to characterize the water-extractable and blood-absorbed constituents of YQQJ. Network pharmacology and molecular docking are further applied to predict and verify the material basis underlying the therapeutic effects of YQQJ against IgAN. The aqueous extract and serum samples of YQQJ were analyzed using UHPLC-Q-Orbitrap HRMS to characterize the chemical constituents and identify blood-absorbed compounds. Compound identification was performed based on reference databases, published literature, and a comprehensive evaluation of retention time, precursor ion mass accuracy, MS/MS fragmentation patterns, and isotopic distribution. Potential targets of the prototype blood-absorbed compounds were predicted using target prediction databases, while IgAN-related targets were collected from integrated bioinformatics platforms. Core targets were screened through PPI network analysis. A "compound-target-pathway-disease" network was constructed to identify key constituents, and molecular docking was performed to evaluate the interactions between core compounds and targets. A total of 185 compounds were identified in the water extract of YQQJ. Among them, 28 compounds entered the bloodstream in their prototype forms. PPI identified 42 core targets associated with YQQJ's therapeutic effects in IgAN. KEGG and GO enrichment analyses showed involvement in cell proliferation, inflammation, and apoptosis, and enrichment in several key pathways such as PI3K-Akt, MAPK, and JAK-STAT. Molecular docking analysis predicted favorable binding interactions between six critical targets (CASP3, IGF1R, JUN, STAT3, PRKCB, and PIK3CA) and three major blood-absorbed compounds-Deacetylasperulosidic acid, Geniposidic acid, and Dioscin -with consistently low binding energies, suggesting potential interactions. This integrated analysis reveals that YQQJ exerts therapeutic effects against IgAN through multiple components and multiple targets. Deacetylasperulosidic acid, Geniposidic acid, and Dioscin are suggested as key active constituents contributing to these effects.