Ginsenoside Rd attenuates blood-brain barrier damage by suppressing proteasome-mediated signaling after transient forebrain ischemia

Ischemic stroke damages the blood-brain barrier (BBB), which leads to brain edema and increases the risk of intracranial hemorrhage. Proteasome inhibition has been found to protect the BBB against cerebral ischemia by suppressing neuroinflammation-mediated matrix metalloproteases-9 (MMP-9) activation. We recently showed that ginsenoside Rd (Rd), a major active ingredient of Panax ginseng, could suppress proteasome-mediated inflammation and be efficient for treating ischemic stroke but downstream mechanisms were still unidentified. For this purpose, Sprague–Dawley rats were subjected to focal cerebral ischemic injury. The activity of proteasome and its downstream effectors nuclear factor-kappa B (NF-κB) and MMP-9 were evaluated. Rd reduced the activity of 20S proteasome in a cell-free assay and inhibited proteasome activity in brain lysates after ischemic stroke. Rd administration suppressed ischemic injury-induced NF-κB activity and IκB degradation mediated by the proteasome. Moreover, Rd reduced the activity and level of MMP-9, a downstream effector of NF-κB, and protected against BBB damage as evidenced by reduced Evan’s Blue leakage and brain edema after cerebral ischemic injury. Jointly, these data demonstrate that ginsenoside Rd attenuates the pathogenesis of cerebral ischemia-induced BBB damage, probably by inhibiting proteasome activity and sequentially suppressing NF-κB/MMP-9 pathway.
Source: NeuroReport - Category: Neurology Tags: Cellular, Molecular and Developmental Neuroscience Source Type: research

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Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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Source: ASAIO Journal - Category: Medical Devices Tags: Adult Circulatory Support Source Type: research
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Source: BMC Neuroscience - Category: Neuroscience Authors: Tags: Research article Source Type: research
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Source: Neurologia i Neurochirurgia Polska - Category: Neurology Authors: Tags: Neurol Neurochir Pol Source Type: research
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Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: EDITORIAL Source Type: research
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Source: Journal of Korean Medical Science - Category: Biomedical Science Tags: J Korean Med Sci Source Type: research
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Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
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Source: Journal of Neurology - Category: Neurology Source Type: research
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Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
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Source: The American Journal of Emergency Medicine - Category: Emergency Medicine Authors: Source Type: research
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