Neuroprotective Effect Of 20(S)-Ginsenoside Rg₃ Against Injury On Cerebral Ischemia

Stroke is the common disease that harms public health seriously. At present, there is no ideal agent to treat this disease clinically. Neuronal ATP-sensitive potassium channels, which couples the energy metabolism with electrical activity of neuron, is the one of the targets of neuroprotective agents. 20(S)-Ginsenoside Rg3 is a chemical compound isolated from the traditional Chinese herb ginseng. In the present study, we investigated the neuroprotective effects of 20(S)-ginsenoside Rg3 against the brain injuries induced by cerebral ischemia and possible pharmacological mechanism.1 Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in ratsGlobal cerebral ischemia/reperfusion and middle cerebral artery occlusion (MCAO) model in male Sprague Dawley rats were employed to determine the neuroprotective effect of 20(S)-ginsenoside Rg3. The results showed that sublingual vein injection of 20(S)-ginsenoside Rg3 at doses of 10 mg·kg^-1 and 5 mg·kg^-1, but not 2.5 mg·kg^-1 exhibited significant neuroprotective effects on rats against cerebral ischemic injury by markedly decreasing the percent of cortical neuronal death and apoptosis, neurological deficit scores, water content of brain, reducing the infarct area. All these findings suggest that 20(S)-ginsenoside Rg3 might provide neuroprotection against the cerebral ischemia induced injury in rat brain.2 Protective effect of 20(S)-ginsenoside Rg3 against oxidative injury on cortical neuronal synaptosomes in rats.NADH-PMS-NBT system to produce O₂^-, EDTANa2-Fe( II )-H2O2 system and Fe2++VitC system to produce OH were available. Rats' cortical neuronalsynaptosomes was prepared for determining the protective effect of 20(S)-ginsenoside Rg3 on oxidative injury. The results showed that 20(S)-ginsenoside Rg3 could not reduce the output of (X and -OH, but could alleviate the injuries of synaptosomes induced by OH.3 Protective effect of 20(S)-ginsenoside Rgj on neuronal damage induced by NMDA(N-methyl-D-aspartate) in cultured rat cortical neurons.Neurotoxity injury induced by NMDA in cultured rat cortical neurons was used to determined the protective effect of 20(S)-ginsenoside Rg3. The different neuroprotective characteristic between 20(S)-ginsenoside Rg3 and MK-801 was investigated. The results showed that 20(S)-ginsenoside Rg3 and MK-801 provide neuroprotection on NMDA-induced cytotoxixity in cultured rat cortical neurons and the neuroprotection of 20(S)-ginsenoside Rg3 but not MK-801 could be nullified by glibenclamide. These data suggested that the protective effect of 20(S)-ginsenoside Rg3 may be related with ATP-sensitive potassium channels.4 Protective effect of 20(S)-ginsenoside Rg$ against rat cortical mitochondrial injuries induced by cerebral ischemiaFocal cerebral ischemia model in rats was employed. Cortical mitochondria was isolated and prepared for the measurement of membrane fluidity, swelling, phospholipid content, respiratory function, activities of mitochondrial respiratory enzymes and superoxide disrnutase (SOD), contents of phospholipid, malondial dehyde (MDA) and Ca2+ to evaluate the function of mitochondrial. The results showed that focal cerebral ischemia resulted in severe neuronal mitochondrial injuries, which could be alleviated by sublingual vein injection of 20(S)-ginsenoside Rg3 at doses of 10 mg-kg"1 and 5 mgkg"1. The swelling of mitochondria was ameliorated, the decomposability of membrane phospholipid was decreased, the membrane fluidity of mitochondria was increased, 20(S)-ginsenoside Rg3 also significantly inhibited the decrease in the activities of respiratory enzymes and SOD of mitochondrial, and theincrease in MDA and Ca2' levels caused by cerebral ischemia in rats. These data suggested that 20(S)-ginsenoside Rg3 showed a protective action against the cortical mitochondrial injuries in rats induced by cerebral ischemia.5 The effect of 20(S)-ginsenoside Rg3 on cerebral blood flow and it's vasodilating characteristicsThe enhanced effect of 20(S)-ginsenoside Rg3 on cerebral blood flow in anesthetic beagle dogs and incomplete global cerebral ischemia rats were measured. Dog basilar artery strips were isolated and suspended in organ chambers for the measurement of vasodilating characteristics of 20(S)-ginsenoside Rg3. The results showed that 20(S)-ginsenoside Rg3 significantly increased the cerebral blood flow in dogs and cerebral ischemia rats. 20(S)-Ginsenoside Rg3 also relaxed the contractions induced by phenylephrine as well as KC1 30 mmolL'1 partially depending on endothelium. The vasodilating effect of 20(S)-ginsenoside Rg3 could be inhibited by synchronously application of glibenclamide. These data showed that the vasodilation mechanism of 20(S)-ginsenoside Rg3 seems to be related with ATP-sensitive potassium channels.6 Effects of 20(S)-ginsenoside Rg3 on Na+, Ca2+, K* channels in cultured primary rat hippocampus neurons.Whole-cell recording technique was used to investigate the effects of 20(S)-ginsenoside Rg3 on cerebral neuronal sodium, calcium and potassium channels. The results showed that 2Q(S)-ginsenoside Rg3 had no significant effect on Na+, Ca2+ currents, but markedly increased the outward K+ currents which could be inhibited by synchronously application of glibenclamide. These data suggested that 20(S)-ginsenoside Rg3 could agonize ATP-sensitive potassium channels.Conclusions:20(S)-ginsenoside Rg3 provides positive effect on cerebral ischemia injuries via inhibiting cortical neuronal and mitochondrial Ca2+ overload, inhibiting injuriesinduced by excitatory amino acid, alleviating oxidative injury, improving the mitochondrial energy metabolism, enhancing cerebral blood flow, and the mechanism may be due to its opening ATP-sensitive potassium channels.