Ginsenoside Rg2 protects PC12 cells against β-amyloid25-35-induced apoptosis via the phosphoinositide 3-kinase/Akt pathway

Alzheimer's disease (AD) is one of the most debilitating neurodegenerative diseases in an aging population. Excessive accumulation of beta-amyloid (A beta) has been proposed as a pivotal event in the pathogenesis of AD. Ginsenoside Rg2 has been reported to exert neuroprotective effects. However, the underlying mechanism for its neuroprotection is not well-understood. In this study, we investigated the protective effects of ginsenoside Rg2 on A beta(25-35)-induced neurotoxicity in PC12 cells and identified a potential molecular signaling pathway involved. The results showed that pretreatment of PC12 cells with ginsenoside Rg2 followed by A beta(25-35) increased cell viability in a concentration-dependent manner compared to cells that were not pretreated. In addition, ginsenoside Rg2 pretreatment attenuated A beta(25-35)- induced increases in the release of lactate dehydrogenase, the intracellular calcium concentration, and levels of reactive oxygen species. Pretreatment with ginsenoside Rg2 increased the Bcl-2/Bax ratio. Moreover, ginsenoside Rg2 attenuated the cleavage of caspase-3 induced by A beta(25-35) thereby improving cell survival. Ginsenoside Rg2 significantly enhanced the phosphorylation of Akt in PC12 cells. Additionally, pretreatment with the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, completely abolished the protective effects of ginsenoside Rg2 against A beta(25-35)-induced neuronal cell apoptosis. These findings unambiguously suggested that the protective effect of ginsenoside Rg2 against A beta(25-35)-induced apoptosis in PC12 cells was associated with enhancement of the PI3K/Akt signaling pathway. (C) 2017 Elsevier B.V. All rights reserved.