1,8-Cineole Promotes the Proliferation of Neural Stem Cells and Inhibits Oxidative Damage Induced by Ischemic Stroke via the Wnt/β-Catenin Signaling Pathway.

Ischemic stroke, characterized by cerebral oxidative injury and compromised neuroregeneration, is a persistent major global health challenge with an ongoing need for novel therapeutic strategies. In this study, we evaluated the neuroprotective potential of 1,8-cineole after ischemic damage, using a photothrombotic stroke model and an H₂O₂-induced oxidative stress paradigm. 1,8-Cineole effectively rescued the morphological integrity and proliferative capacity of oxidative stress-impaired C17.2 neural stem cells (NSCs). In vivo, treatment with 1,8-cineole markedly improved motor coordination and behavioral outcomes in mice subjected to middle cerebral artery occlusion (MCAO), as demonstrated by enhanced performance on rotarod and open-field tests. Mechanistic analyses, including immunofluorescence and western blotting, revealed that 1,8-cineole activates the Wnt/β-catenin signaling pathway, leading to the upregulation of key mediators such as Wnt3a, Cyclin D1, and β-catenin. These molecular alterations correlated with increased NSC proliferation and promoted neural repair after cerebral ischemia. Our results indicate that 1,8-cineole represents a promising therapeutic candidate for stroke, exerting its effects via the restoration of redox balance and the facilitation of Wnt-driven neuroregeneration. This dual-action strategy mitigates acute oxidative injury while enhancing endogenous repair pathways, providing a novel framework for multitarget interventions in stroke recovery. Further studies are warranted to elucidate the pharmacokinetic profile and translational potential of this compound.