Prevention of Ischemic Neuronal Death by Intravenous Infusion of a Ginseng Saponin, Ginsenoside Rb1, That Upregulates Bcl-xL Expression
| Autor: | Kohji Sato, Keiichi Samukawa, Noriaki Mitsuda, Masahiro Sakanaka, Ryuji Hata, Pengxiang Zhu, Bo Zhang, Lihua Yang, Hiroko Fujita, Junya Tanaka, Nobuji Maeda, Tong Chun Wen |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Programmed cell death Ginsenosides bcl-X Protein Ischemia Panax Blood Pressure Bcl-xL Pharmacology Nitric Oxide Neuroprotection Brain Ischemia Brain ischemia Lesion chemistry.chemical_compound Ginseng Rats Inbred SHR STAT5 Transcription Factor medicine Animals Humans Maze Learning Cerebral Cortex Neurons Behavior Animal Cell Death Molecular Structure biology business.industry Infarction Middle Cerebral Artery medicine.disease Rats Neuroprotective Agents Neurology chemistry Ginsenoside Anesthesia biology.protein Neurology (clinical) medicine.symptom Gerbillinae Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 26:708-721 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/sj.jcbfm.9600225 |
| Popis: | Almost all agents that exhibit neuroprotection when administered into the cerebral ventricles are ineffective or much less effective in rescuing damaged neurons when infused into the blood stream. Search for an intravenously infusible drug with a potent neuroprotective action is essential for the treatment of millions of patients suffering from acute brain diseases. Here, we report that postischemic intravenous infusion of a ginseng saponin, ginsenoside Rb1 (gRb1) (C54H92O23, molecular weight 1109.46) to stroke-prone spontaneously hypertensive rats with permanent occlusion of the middle cerebral artery distal to the striate branches significantly ameliorated ischemia-induced place navigation disability and caused an approximately 50% decrease in the volume of the cortical infarct lesion in comparison with vehicle-infused ischemic controls. In subsequent studies that focused on gRb1-induced expression of gene products responsible for neuronal death or survival, we showed that gRb1 stimulated the expression of the mitochondrion-associated antiapoptotic factor Bcl-xL in vitro and in vivo. Moreover, we revealed that a Stat5 responsive element in the bcl-x promoter became active in response to gRb1 treatment. Ginsenoside Rb1 appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other diseases involving activation of mitochondrial cell death signaling. |
| Databáze: | OpenAIRE |
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