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Updated: Feb 1, 2026

Optimized Management of Endovascular Treatment for Acute Ischemic Stroke
Published on: January 18, 2018
Discovery of Novel Natural Product-Based PDE4 Inhibitors for Ischemic Stroke Treatment without Emetogenicity at
Chuang Xia1,2, Mingjia Yu3, Yujie Ni1
1Innovation Program of Drug Research on Neurological and Metabolic Diseases, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Abstract:
Phosphodiesterase-4 (PDE4) inhibitors show potential for treating ischemic stroke, but are often constrained by emesis or low blood-brain barrier (BBB) permeability. To overcome these challenges, this paper developed novel PDE4 inhibitors via AI-driven structural evolution of natural antistroke products and identified the Phthalide derivative B05 as a PDE4 inhibitor exhibiting excellent selectivity (selectivity index > 420), favorable pharmacological properties (F = 15.5%), and good BBB permeability. Significantly, B05 did not induce vomiting at ultrahigh doses (60 mg/kg), a significant advantage over conventional PDE4 inhibitors. B05 protected neuronal cells from oxygen-glucose deprivation and reoxygenation-induced injury. Additionally, in the middle cerebral artery occlusion and reperfusion model, B05 significantly reduced infarct volume, preserved BBB integrity, attenuated cerebral edema, inhibited astrocyte and microglial activation, prevented ischemia-induced neuronal apoptosis, and improved poststroke motor function and cognitive performance. These findings support the potential of B05 as a promising candidate for the treatment of ischemic stroke.
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