OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction (DTD) on ischemic stroke.

METHODS A mouse middle cerebral artery occlusion (MCAO) model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury. DTD was gavaged once a day for 3 days after MCAO. Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.

RESULTS In the MCAO model, DTD treatment significantly reduced infarct volume (P < 0.01) and attenuated blood-brain barrier disruption, as evidenced by decreased IgG leakage and preserved laminin expression (P < 0.05). Furthermore, DTD suppressed neutrophil infiltration into ischemic brain tissue, as demonstrated by reduced neutrophil elastase (P < 0.01) and myeloperoxidase (P < 0.05) levels. Mechanistically, DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B (PDE4B), a key regulator of neutrophil migration (P < 0.05). Molecular docking analysis identified four active DTD components-apigenin, vitexin, chlorogenic acid, and orientin-with strong binding affinities to PDE4B (binding energies < -5 kcal·mol^-1), suggesting their potential role in mediating DTD's therapeutic effects.

CONCLUSION These findings highlight DTD as a promising intervention for ischemic stroke, targeting NVU preservation and PDE4B-dependent neutrophil modulation.