Potential Protective Effects of Quercetin on Acute Kidney Injury: An Integrated Study of Network Pharmacology, GEO Database, and Experimental Validation

This study explored the active components and mechanisms of Cistanche deserticola Ma (CH) in treating acute kidney injury (AKI) using network pharmacology, GEO data, and experimental validation. Active compounds and targets of CH were identified from TCMSP, SwissTargetPrediction, and Herb databases. AKI-related genes were sourced from GeneCards, OMIM, and GEO. A protein-protein interaction (PPI) network of overlapping targets was constructed via STRING, with key nodes ranked using CytoNCA. GO/KEGG enrichment was performed in R, and a target-pathway network was built in Cytoscape. Molecular docking was conducted with Discovery Studio and visualized in Pymol. In vitro assays, including MTT, flow cytometry, and Western blotting, validated quercetin’s effects on LPS-induced HK-2 cell injury. Five active CH compounds and 397 potential targets were identified, with 221 overlapping AKI targets. Core targets included TP53, IL-6, AKT1, EGFR, TNF, and SRC. Enrichment analysis highlighted the PI3K/AKT pathway, apoptotic regulation, and xenobiotic response. Quercetin showed strong binding to core targets and reduced apoptosis via PI3K/AKT inhibition in vitro. CH may protect against AKI through PI3K/AKT pathway modulation, supporting its therapeutic potential.