PROTECTION OF ISCHEMIC HIPPOCAMPAL-NEURONS BY GINSENOSIDE RB-1, A MAIN INGREDIENT OF GINSENG ROOT

Our previous study showed that the oral administration of red ginseng powder before but not after transient forebrain ischemia prevented del ayed neuronal death in gerbils, and that a neuroprotective molecule wi thin red ginseng powder was ginsenoside Rb-1. However, it remains to b e clarified whether or not ginsenoside Rb-1 acts directly on the ische mic brain, and the mechanism by which ginsenoside Rb-1 protects the is chemic CA1 neurons is not determined. Without elucidation of the pharm acological property of ginsenoside Rb-1, the drug would not be accepte d as a neuroprotective agent. The present study demonstrated that the intracerebroventricular infusion of ginsenoside Rb-1 after 3.5 min or 3 min forebrain ischemia, precluded significantly the ischemia-induced shortening of response latency in a step-down passive avoidance task and rescued a significant number of hippocampal CA1 neurons from letha l ischemic damage. The intracerebroventricular infusion of ginsenoside Rb-1 did not affect hippocampal blood flow or hippocampal temperature except that it caused a slight increase in hippocampal blood flow at 5 min after transient forebrain ischemia. Furthermore, ginsenoside Rb- 1 at concentrations of 0.1-100 fg/ml (0.09-90 fM) rescued hippocampal neurons from lethal damage caused by the hydroxyl radical-promoting ag ent FeSO4 in vitro, and the Fenton reaction system containing p-nitros odimethylaniline confirmed the hydroxyl radical-scavenging activity of ginsenoside Rb-1. These findings suggest that the central infusion of ginsenoside Rb-1 after forebrain ischemia protects hippocampal CA1 ne urons against lethal ischemic damage possibly by scavenging free radic als which are overproduced in situ after brain ischemia and reperfusio n. The present study may validate the empirical usage of ginseng root over thousands of years for the prevention of cerebrovascular diseases . (C) 1997 Elsevier Science Ireland Ltd.