Edaravone-Dexborneol (EDB) is a rationally engineered neuroprotective formulation that integrates the free-radical scavenger edaravone with the monoterpenoid (+)-borneol in a multimodal 4:1 M ratio. This combination was developed to overcome the translational limitations of single-target neuroprotectants by combining potent antioxidative activity with enhanced blood-brain barrier permeability, anti-inflammatory signaling, and improved pharmacokinetic behavior. This review provides a mechanistic synthesis of the multimodal pharmacology of EDB, emphasizing its associated modulation of oxidative stress, neuroinflammation, and regulated cell death pathways-including apoptosis, pyroptosis, and, in particular, ferroptosis. A structured search of preclinical and clinical literature was conducted, and study quality was appraised using established methodological frameworks to ensure a rigorous and comprehensive synthesis. Across clinical investigations, EDB consistently demonstrates superior neurological recovery and functional outcomes compared with edaravone monotherapy. Mechanistically, EDB treatment is accompanied by activation of the Nrf2/HO-1/SLC7A11 signaling cascade, concurrent with upregulation of GPX4 and reduction of iron-dependent lipid peroxidation, pointing toward a key role in mitigating ferroptotic cell death. In parallel, EDB is associated with attenuated neuroinflammatory signaling via downregulation of the TLR4/MyD88/NF-κB cascade and suppression of NLRP3 inflammasome activation. These actions are correlated with microglial polarization toward an M2 reparative phenotype, stabilization of the neurovascular unit, and reduced blood-brain barrier disruption. Collectively, the clinical and mechanistic evidence highlights EDB as a promising combination therapy that targets the intersection of oxidative stress, inflammation, and regulated cell death, providing a compelling rationale for its therapeutic potential for acute and chronic central nervous system disorders.
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