Abstract
BackgroundIn this study, we investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules.MethodsMale Sprague-Dawley rats were induced focal cerebral ischemia by a transient middle cerebral artery occlusion (tMCAO) for 90 min, and then orally administrated with the water extract of A. gigas hairy roots (AG). After 24 h reperfusion, infarction volume and the changes of BBB permeability were measured by TTC and Evans Blue (EB) staining. The neuronal cell damage and the activation of glial cells were assessed by immunohistochemistry in the ischemic brain. The expression of angiogenesis-induced proteins such as angiopoietin-1 (Ang-1), and vascular endothelial growth factor (VEGF), inflammatory protein such as intercellular adhesion molecule-1 (CAM-1), tight junction proteins such as ZO-1, and Occludin and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT were determined in the ischemic brains by Western blot, respectively.ResultsThe treatment of AG extract significantly decreased the volumes of brain infarction, and edema in MACO-induced ischemic rats. AG extract decreased the increase of BBB permeability, and neuronal death and inhibited the activation of astrocytes and microglia in ischemic brains. AG extract also significantly increased the expression of Ang-1, Tie-2, VEGF, ZO-1 and Occludin through activation of the PI3K/Akt pathway. AG extract significantly increased the expression of ICAM-1 in ischemic brains.ConclusionsOur results indicate that the hairy root of AG has a neuroprotective effect in ischemic stroke.
Highlights
In this study, we investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules
Effect of A. gigas (AG) extract on brain infarction To evaluate the neuroprotective effect of AG extract on ischemic damages, we measured the infarction volumes in MCAO-induced ischemic rats by triphenyltetrazolium chloride (TTC) staining
Effect of AG extract on ischemic damages in neuronal cells To evaluate the neuroprotective effect of AG extract on ischemic neuronal damages, we investigated the morphological changes of neuronal cells in the ischemic hemisphere of MCAO-induced ischemic rats
Summary
We investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules. Oh et al BMC Complementary and Alternative Medicine (2015) 15:101 to 24 hours Cerebral injury affects both of the BBB and autoregulation because the extent of flow during reperfusion and is these are correlated with neurological injury. Cerebral inflammation can eventually disrupt the BBB further by more extensive activation of resident cells like astrocytes and microglia, and infiltration of inflammatory cells, macrophages and leukocytes. As brain injury triggers the inflammatory response and aggravates the injury, the decreased expression of TNF-α and ICAM-1 indicate a diminished progression of injury. Recent experimental studies show that systemic inflammation exacerbates neutrophil infiltration in the brain, altering the kinetics of the BBB tight junction disruption after experimental stroke in mice [11]. A transformation from transient to sustained BBB disruption caused by enhanced neutrophil-derived neurovascular MMP-9 is a critical mechanism underlying the exacerbation of ischemic brain injury by systemic inflammation, mediated through conversion of a transient to a sustained disruption of the tight junction protein [12]
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