1. ¹Department of Integrated Basic Medical Science, Division of Functional Histology, Ehime University School of Medicine, Shitukawa, Toon, Ehime, Japan
2. ²Department of Integrated Basic Medical Science, Division of Organ Physiology, Ehime University School of Medicine, Shitukawa, Toon, Ehime, Japan

Correspondence: Drs R Hata and M Sakanaka, Department of Integrated Basic Medical Science, Division of Functional Histology, Ehime University School of Medicine, Shitukawa, Toon, Ehime 791-0295, Japan. E-mail: hata@m.ehime-u.ac.jp and Sakanaka@m.ehime-u.ac.jp

Received 6 May 2005; Revised 29 July 2005; Accepted 11 August 2005; Published online 14 September 2005.

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-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 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.