Work

A Network Pharmacology-Based Investigation into the Mechanism of Quercetin Combined with Rosuvastatin in Delaying Diabetic Nephropathy via Inhibiting NRK-52E Cell Ferroptosis

Year: 2025

Type: article

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.

Source: Diabetes Metabolic Syndrome and Obesity

DOI: 10.2147/dmso.s524983

Authors: Meishe Gan, Zhiyuan Lin, Junxue Ma, Ning Li, Biaoliang Wu

Institutions: Guangxi Medical University, Tumor Hospital of Guangxi Medical University, Youjiang Medical College for Nationalities, Affiliated Hospital of Youjiang Medical University for Nationalities

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836