Multifaceted regulatory effects of quercetin on cell death pathways: apoptosis, ferroptosis, pyroptosis, and autophagy

Cell death regulation is pivotal for maintaining physiological homeostasis and combating pathological conditions. Quercetin, a natural flavonoid, exhibits significant therapeutic potential by modulating diverse regulated cell death pathways, including apoptosis, ferroptosis, pyroptosis, and autophagy. This review synthesizes current evidence on quercetin’s mechanisms in suppressing apoptosis via caspase inhibition and ROS scavenging, mitigating ferroptosis through GPX4 upregulation and lipid peroxidation reduction, attenuating pyroptosis by NLRP3 inflammasome inhibition, and regulating autophagy to balance cell survival and death. Evidence from models demonstrates its efficacy in alleviating ischemic injuries, neurodegenerative disorders, inflammatory diseases, and cancer via key pathways including Nrf2/HO-1, Sirt1/p53/SLC7A11, TLR4/NF-κB/NLRP3, and mTOR. These findings underscore quercetin’s multi-targeted therapeutic potential, positioning it as a promising candidate for treating diseases linked to dysregulated cell death.