Chunghyul-dan, a multi-botanical ethanol extract, improves collateral perfusion and neurovascular stability in permanent focal cerebral ischemia

초록

Background: Collateral perfusion and neurovascular stability critically influence outcomes after ischemic stroke; however, no pharmacological agent is currently approved to enhance these processes.Objectives: Chunghyul-dan (CHD), a standardized multi-botanical ethanol extract with reported vascular and anti-inflammatory properties, was evaluated for its neurovascular protective effects in a permanent middle cerebral artery occlusion (pMCAO) mouse model.The Process and Methods: Male ICR mice subjected to pMCAO received oral Chunghyul-dan (30–120 mg/kg). Cortical infarct volume, anterior cerebral artery perfusion, angiogenesis-related signaling, neuroinflammation, and endothelial barrier integrity were assessed using histological analysis, laser Doppler flowmetry, immunohistochemistry, and complementary in vitro studies in BV2 microglia and bEND.3 endothelial cells.Results: CHD significantly reduced cortical infarct volume, with maximal protection observed at 60 mg/kg. Laser Doppler analysis demonstrated enhanced ACA perfusion at 30 mg/kg during early ischemia. CHD upregulated VEGF expression in ischemic cortex and endothelial cells, supporting vascular remodeling. Neuroinflammation was attenuated, as CHD reduced Iba-1–positive microglial activation and suppressed iNOS, IL-6, and TNF-α expression. Endothelial barrier integrity was preserved through reduced PECAM-1 expression, restoration of claudin-5 and occludin, and selective inhibition of STAT3 phosphorylation, whereas TLR4/MAPK signaling remained unchanged.Conclusion: CHD confers multi-level neurovascular protection by promoting collateral perfusion, facilitating VEGF-associated vascular adaptation, suppressing neuroinflammation, and stabilizing endothelial junctional architecture. These findings support further translational evaluation of CHD as a pharmacological modulator of collateral circulation in ischemic stroke.

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