A Network Pharmacology-Based Investigation into the Mechanism of Quercetin Combined with Rosuvastatin in Delaying Diabetic Nephropathy via Inhibiting NRK-52E Cell Ferroptosis.
Meishe Gan, Zhiyuan Lin, Junxue Ma, Ning Li, Biaoliang Wu
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引用次数: 0
Abstract
Objective: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and current therapeutic options are limited in effectively managing DN progression. Renal tubular epithelial cell (RTEC) ferroptosis has emerged as a critical mechanism contributing to DN pathogenesis. This study aimed to investigate the potential synergistic effects of quercetin (QCT) and rosuvastatin (RSV) on inhibiting RTEC ferroptosis and ameliorating DN progression, providing a novel combinatorial therapeutic strategy.
Methods: Public database data were analyzed using network pharmacology to identify QCT-DN-related and RSV-DN-related targets, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. NRK-52E cells were cultured in vitro under high glucose conditions (30 mM glucose) to induce damage, then incubated with QCT and/or RSV. Enzyme-linked immunosorbent assay measured inflammatory cytokines (IL-6, TGF-β, TNF-α), flow cytometry detected reactive oxygen species (ROS), and colorimetric assays quantified superoxide dismutase (SOD), malondialdehyde (MDA), and iron ions. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) evaluated ferroptosis-related genes (GPX4, SLC7A11).
Results: Network pharmacology analysis revealed primary enrichment of both QCT-DN-related and RSV-DN-related targets in ferroptosis-related pathways. In vitro cell experiments showed that both QCT and RSV, when used individually, significantly inhibited the expression of inflammatory cytokines (IL-6, TGF-β, and TNF-α), ROS generation, SOD levels, MDA levels, iron ion levels, and the expression of ferroptosis-related genes (GPX4 and SLC7A11) in NRK-52E cells under high-glucose conditions. Furthermore, compared to the individual use of QCT or RSV, the combined use of QCT and RSV demonstrated a more significant inhibitory effect on the inflammatory phenotype and ferroptosis levels in NRK-52E cells.
Conclusion: This study highlights the potential of combining QCT and RSV for DN management. Network pharmacology confirmed associations between QCT/RSV targets and NRK-52E cell ferroptosis. In vitro experiments validated superior protective effects of co-treatment over individual treatments, warranting further in vivo investigation.
期刊介绍：
An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.
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