Quercetin inhibits silica nanoparticle-induced ferroptosis and inflammation by alleviating oxidative stress and targeting STAT3 in brain.

Nanoscale silicon dioxide (SiO2) is a non-metallic oxide material, which is used in biomedicine and biological industry. After being ingested, SiO2 will produce deposits in the body, which will cause harm. Quercetin (QUE), as a flavonoid compound, has anti-inflammatory effects. However, it is still unclear whether QUE inhibits SiO2 exposion-induced ferroptosis in mouse brain tissue by alleviating oxidative stress and targeting STAT3. In this experiment, SiO2 and/or QUE exposed mice and NS20Y cell models were established, while MIX plus ROS activator and STAT3 activator were established. HE, TEM, qRT-PCR, immunofluorescence and Western blot were used to detect the related indicators. SiO2-induced oxidative stress in brain tissue and nerve cells of mice activates JAK/STAT3 signaling pathway. Activation of this pathway leads to an imbalance in mitochondrial homeostasis, which ultimately triggers ferroptosis and inflammation. Moreover, the introduction of QUE can effectively alleviate the above phenomena. Furthermore, we confirmed the targeting relationship between QUE and STAT3. These results suggest that QUE alleviates SiO2-induced ferroptosis and inflammation in nerve cells by regulating oxidative stress and targeting STAT3. The results enrich the toxicology research of SiO2, but also provide a basis for the prevention and control of SiO2 toxicity from the perspective of macromolecular targeting.