title: Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb(1), that upregulates Bcl-x(L) expression.
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 Rb(1) (gRb(1)) (C(54)H(92)O(23), 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 gRb(1)-induced expression of gene products responsible for neuronal death or survival, we showed that gRb(1) stimulated the expression of the mitochondrion-associated antiapoptotic factor Bcl-x(L) in vitro and in vivo. Moreover, we revealed that a Stat5 responsive element in the bcl-x promoter became active in response to gRb(1) treatment. Ginsenoside Rb(1) 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.
authors.affiliation: Department of Integrated Basic Medical Science, Division of Functional Histology, Ehime University School of Medicine, Shitukawa, Toon, Ehime, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hata
authors.forename: Pengxiang
authors.initials: P
authors.lastname: Zhu
authors.forename: Kohji
authors.initials: K
authors.lastname: Sato
authors.forename: Tong-Chun
authors.initials: TC
authors.lastname: Wen
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fujita
authors.forename: Noriaki
authors.initials: N
authors.lastname: Mitsuda
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
authors.forename: Keiichi
authors.initials: K
authors.lastname: Samukawa
authors.forename: Nobuji
authors.initials: N
authors.lastname: Maeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakanaka
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology*; D016923:Cell Death / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005849:Gerbillinae; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018782:Maze Learning; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D051381:Rats; D011918:Rats, Inbred SHR; D050799:STAT5 Transcription Factor / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D036145:Ginsenosides; D018696:Neuroprotective Agents; D050799:STAT5 Transcription Factor; D051020:bcl-X Protein; D009569:Nitric Oxide