Multitarget natural compounds taming NETosis: A translational strategy for cancer and inflammatory diseases

Neutrophil extracellular traps (NETs) play dual roles in host defense and disease pathogenesis. Dysregulated NETosis contributes to chronic inflammation, thrombosis, and cancer metastasis, highlighting its therapeutic relevance. This review delineates the molecular mechanisms governing NETosis, emphasizing pathological consequences in autoimmune disorders, sepsis, and tumor microenvironments. We spotlight natural compounds as multitarget modulators of NETosis. These agents inhibit key trigger and signaling cascades, while preserving antimicrobial functions. Further, we propose a high-throughput molecular docking strategy to identify NETosis-targeting natural products, offering a roadmap for drug development. By bridging mechanistic insights and translational potential, this work underscores natural compounds as promising therapeutics for NET-driven pathologies.