It indicates the astrocytes activation in the D-gal-induced aged brain. Moreover, for the increased levels of Aeg1, it was also consistent with the morphological characteristic of activated astrocytes in the D-gal-administration group. However, Nestin and Aeg1 expression was down-regulated in the D-gal-administration plus Rg1 treatment group, indicating that the reactive astrogliosis induced by D-gal was alleviated by Rg1 treatment. This result further illustrated that Rg1 could protect the age-related NSCs/ NPCs survival and reduce astrogenesis. Cognitive capacity was improved, neurogenesis was restored and reactive astrogliosis was attenuated by ginsenoside Rg1 treatment to D-gal administered rats. We did not elucidate the direct mechanism of Rg1 on these effects in the hippocampus. However, we assumed two possible mechanisms for these effects. One of these is the antioxidant function of Rg1 on the hippocampus, because the oxygen metabolism of D-gal produces many reactive oxygen species and may impair learning and memory directly or indirectly. In addition, ROS can potently inhibit neurogenesis and particularly NSCs/NPCs proliferation. Oxidative damage can also affect glial cells, which are connected to neuronal death or decreases in neuronal proliferation. In the present study, Rg1 treatment protected the hippocampus against oxidative stress by promoting the activities of SOD and GSH-Px, which are important anti-oxidative enzymes to remove the oxidative stress accumulated in aging. On the other hand, as the telomere is highly sensitive to the oxidative stress, the increased telomere length and telomerase activities in the D-gal-administration plus Rg1 treatment group may also be due to the effect of the anti-oxidant function of Rg1. These results suggest that ginsenoiside Rg1 effectively attenuates D-gal-induced oxidative damage in the hippocampus, possibly by eliminating free radicals through activating antioxidant enzymes. It should be noted that the activities of SOD and GSH-Px were remarkably increased in the Rg1 single-treated rats. It confirmed the anti-oxidative effect of ginsenoside Rg1, which was consistent with previous studies. Oxidative stress has been implicated in BAY 73-4506 msds proinflammation, and aging is also associated with inflammation. When chronic inflammation occurs in the aged brain, a variety of neurotoxic products and proinflammatory cytokines such as IL-1b, IL-6, and TNF-a are released. In the present study, Rg1 treatment significantly reduced the levels of IL-1b, IL-6, and TNF-a, compared with the D-gal administration group. It suggests that Rg1 can protect the hippocampus from age-induced chronic inflammation. Furthermore, the elevated levels of proinflammatory cytokines could also be a consequence of astrocytes activation. Sustained activation of astrocytes releases high amount of NO and proinflammatory cytokines which accumulate in aging process, to exacerbate neuronal impairments. In this study, the attenuated activation status of astrocytes by the Rg1 therapy may be a combined outcome of the anti-inflammation and the neurogenesis-promoting capacity of ginsenoside Rg1.