Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb1, that upregulates Bcl-xL expression

Bo Zhang, Ryuji Hata, Pengxiang Zhu, Kohji Sato, Tong Chun Wen, Lihua Yang, Hiroko Fujita, Noriaki Mitsuda, Junya Tanaka, Keiichi Samukawa, Nobuji Maeda, Masahiro Sakanaka

研究成果: Article

56 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)708-721
ページ数14
ジャーナルJournal of Cerebral Blood Flow and Metabolism
26
発行部数5
DOI
出版物ステータスPublished - 01-05-2006

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Panax
Saponins
Intravenous Infusions
Up-Regulation
Stroke
Cerebral Ventricles
Middle Cerebral Artery Infarction
Brain Diseases
Acute Disease
Inbred SHR Rats
Therapeutics
Mitochondria
Cell Death
Ischemia
Molecular Weight
ginsenoside Rb1
Gene Expression
Neurons
Survival
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

これを引用

Zhang, Bo ; Hata, Ryuji ; Zhu, Pengxiang ; Sato, Kohji ; Wen, Tong Chun ; Yang, Lihua ; Fujita, Hiroko ; Mitsuda, Noriaki ; Tanaka, Junya ; Samukawa, Keiichi ; Maeda, Nobuji ; Sakanaka, Masahiro. / Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb1, that upregulates Bcl-xL expression. :: Journal of Cerebral Blood Flow and Metabolism. 2006 ; 巻 26, 番号 5. pp. 708-721.
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abstract = "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.",
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Zhang, B, Hata, R, Zhu, P, Sato, K, Wen, TC, Yang, L, Fujita, H, Mitsuda, N, Tanaka, J, Samukawa, K, Maeda, N & Sakanaka, M 2006, 'Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb1, that upregulates Bcl-xL expression', Journal of Cerebral Blood Flow and Metabolism, 巻. 26, 番号 5, pp. 708-721. https://doi.org/10.1038/sj.jcbfm.9600225

Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb1, that upregulates Bcl-xL expression. / Zhang, Bo; Hata, Ryuji; Zhu, Pengxiang; Sato, Kohji; Wen, Tong Chun; Yang, Lihua; Fujita, Hiroko; Mitsuda, Noriaki; Tanaka, Junya; Samukawa, Keiichi; Maeda, Nobuji; Sakanaka, Masahiro.

:: Journal of Cerebral Blood Flow and Metabolism, 巻 26, 番号 5, 01.05.2006, p. 708-721.

研究成果: Article

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T1 - Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb1, that upregulates Bcl-xL expression

AU - Zhang, Bo

AU - Hata, Ryuji

AU - Zhu, Pengxiang

AU - Sato, Kohji

AU - Wen, Tong Chun

AU - Yang, Lihua

AU - Fujita, Hiroko

AU - Mitsuda, Noriaki

AU - Tanaka, Junya

AU - Samukawa, Keiichi

AU - Maeda, Nobuji

AU - Sakanaka, Masahiro

PY - 2006/5/1

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