Ginsenoside Rb1Attenuates Chronic Hypobaric Hypoxia-Induced Cognitive Deficits

Senile dementia, a slowly progressive neurodegenerative disorder characterized bysevere memory loss and cognitive impairment, has become a major public health issue asthe proportion of elder increases in the population. Vascular dementia （VD）, as thesecond most common form of dementia, accounts for approximately20to30%ofdementia cases1. At present, no specific drug exists to prevent, delay, or cure VD.Bilateral permanent occlusion of the common carotid arteries （2-VO） in rats results in asignificant reduction in cerebral blood flow. Therefore, it is a well-characterized model toinvestigate the cognitive consequences of chronic cerebral hypoperfusion2. This animalmodel exhibits learning and memory impairments resembling those found in VD,accompanied by neuronal degeneration and microvascular abnormalities3. Several studies,especially pharmacological study, based on this model were designed to test potentiallybeneficial strategies to prevent, delay, or cure the progression of dementia associatedwith reduced cerebral blood flow. Ginseng is a popular medicinal plant used in traditional Chinese medicine systemfor a long time. Ginsenoside Rb₁is the main bioactive ingredients isolated from Ginseng.Modern pharmacological studies indicated that Ginsenoside Rb₁had variouspharmacological properties, including neuroprotective effect, anti apoptosis andanti-oxidative effects. Recently, Ginsenoside Rb₁was reported to be capable ofprotecting rats against cognitive deficits and oxidative stress induced by epilepsia. So wehypothesis that Ginsenoside Rb₁might be a potential therapeutic agent for treating orpreventing VD. In order to provide a new window into the pharmacological properties ofGinsenoside Rb₁, the present study was designed to investigate the treatment effects ofGinsenoside Rb₁on cognitive dysfunction caused by chronic cerebral hypoperfusion andtry to explore the possible mechanism.MethodsRat were randomly divided into3groups(n=20.（1） Control group: Sham operationrats treated with normal saline;（2） Model group:2-VO rats treated with normal saline;（3）Ginsenoside Rb₁group:2-VO rats treated with Ginsenoside Rb₁. Daily intraperitonealinjection of Ginsenoside Rb₁（twice per day,2mg/kg day） or vehicle （normal saline） wasstarted on the surgery day, and lasted for the termination of the experiment on day28.Firstly, cognitive function was evaluated using the Morris water maze and hippocampalLTP. Then, neuronal apoptosis of hippocampus in different group were compared. Andthen, SOD, GSH-PX, GSH, MDA of hippocampus in different group were detecttedResultsBoth cognitive deficits and LTP inhibition in hippocampal CA1caused by chroniccerebral hypoperfusion were markedly improved after administration of Ginsenoside Rb₁for4weeks. Western blot analyses indicated that Ginsenoside Rb₁inhibited activation ofcaspase-3and prevented increase of Bax/Bcl-2ratio in the hippocampus. Furtherexperiments proved that SOD, GSH-PX and GSH were increased by Ginsenoside Rb₁, and MDA wae decreased by Ginsenoside Rb₁. These findings indicated that Ginsenoside Rb₁attenuated cognitive deficits caused by chronic cerebral hypoperfusion, and itsanti-apoptotic action might be involved in the therapeutic effect.ConclusionGinsenoside Rb₁attenuated cognitive deficits caused by chronic cerebralhypoperfusion, and its anti apoptosis and anti-oxidative effects might be involved in thetherapeutic effect.