Naringenin inhibits ferroptosis to reduce radiation-induced lung injury: insights from network Pharmacology and molecular docking

作者：Junlin Jiang, Xianhui Deng, Chen-Han Xu, Yaxian Wu, Jian-feng Huang · 发表于：Pharmaceutical Biology · 年份：2025 · DOI：10.1080/13880209.2025.2465312 · 被引用次数：23 · 研究领域：Medicine

Abstract Context Naringenin is a natural flavanone with potent pharmacological properties. It has demonstrated therapeutic potential in treating various diseases and organ injuries, including radiation-induced lung injury (RILI). Ferroptosis is a newly type of cell death, and naringenin has been shown to attenuates ferroptosis. Objective To evaluate the inhibitory effect and molecular mechanism of naringenin on ferroptosis during RILI process. Materials & methods Firstly, BEAS-2B and HUVECs cells were pre-incubated with naringenin for 1 h prior to 8 Gy of X-ray irradiation to evaluate oxidative stress, inflammation, and the mRNA levels of ferroptosis-related genes. Next, target genes of naringenin, RILI, and ferroptosis were identified using the TCMSP, SwissTargetPrediction, and GeneCards databases. The target network was constructed with Cytoscape and STRING. Finally, the core target genes were identified through in vitro experiments by qRT-PCR, western blot and immunofluorescence staining. Results Naringenin effectively reduced radiation-induced increasement of oxidative stress, inflammation, and ferroptosis markers in both cell lines. Network pharmacology identified 14 target genes, with prostaglandin endoperoxide synthase (PTGS2) and Valosin-containing protein (VCP) mRNA levels being prominent, which were crucial for ferroptosis regulation. Molecular docking revealed strong binding interactions between naringenin and the two target proteins. Subsequently, experimental val...