Plants and Plant‐Derived Compounds Mediate Protection Across Diverse Pathological Conditions by Targeting the <scp>PANoptosis</scp> Pathways

PANoptosis is a complex inflammatory programmed cell death pathway that integrates the key mechanistic features of pyroptosis, apoptosis, and necroptosis. It represents a crucial innate immune mechanism for eliminating infected or damaged cells; however, its dysregulation is implicated in the pathogenesis of a wide spectrum of diseases, including sepsis, myocardial infarction, acute organ injuries, and cancer. Consequently, targeting PANoptosis has garnered significant interest as a novel therapeutic strategy. This review explored the potent modulatory effects of herbal medicines and their bioactive compounds on PANoptotic pathways. Preclinical evidence indicated that numerous plant-derived compounds (including, costunolide, artemetin, lycopene, amentoflavone, sulforaphane, licochalcone B, hesperidin, apigenin, and diosmin) and traditional formulations (such as Danggui Buxue, Xian Ling Gu Bao decoction, Xiao Chai Hu decoction, Dachaihu decoction, and Dachengqi decoction dispensing granule) can effectively suppress the core molecular drivers of PANoptosis, such as caspase-1, caspase-3, caspase-8, RIPK1, RIPK3, MLKL, and GSDMD, alongside key inflammasome components like NLRP3. Their mechanisms of action are multi-faceted, encompassing the downregulation of upstream sensors (e.g., ZBP1), the attenuation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), and the enhancement of cellular antioxidant defenses via the Nrf2 pathway and enzymes like SOD and CAT. By inhibiting PANoptosis, these natural products demonstrate substantial protective potential across diverse models of cardiovascular, pulmonary, renal, hepatic, and neurological diseases.