Korean Red Ginseng Inhibits Amyloid-β-Induced Apoptosis and Nucling Expression in Human Neuronal Cells

Introduction: The accumulation of amyloid-β (Aβ) plaque in the brain is a characteristic feature of Alzheimer's disease (AD) and the cause of fatal oxidative damage to neuronal cells. Korean red ginseng (RG) is used extensively in traditional medicine and is known to have anti-oxidative and anti-inflammatory properties. Objective: This study aims to investigate whether Korean RG extract inhibits Aβ-induced neuronal apoptosis. Methods: Human neuronal cells (SH-SY5Y cells) were stimulated with Aβ (5 μmol/L) and treated with RG dissolved in phosphate-buffered saline (0.2, 2, 20 μg/mL). Results: RG suppressed the reduction of cell viability and the increase in apoptotic factors (Bax/Bcl-2 ratio and caspase-3 activity) in Aβ-treated cells. RG suppressed Aβ-induced increases in intracellular and mitochondrial reactive oxygen species (ROS) levels and mitochondrial dysfunction (determined by low mitochondrial membrane potential and oxygen consumption rate) in a dose-dependent manner. RG inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) activation and expression of the pro-apoptotic gene Nucling in Aβ-treated cells. Conclusion: RG confers protection against neuronal apoptosis by reducing ROS levels and suppressing mitochondrial dysfunction and NF-κB activation, which results in suppression of NF-κB-mediated activation of Nucling expression in Aβ-treated cells. Supplementation with RG may be beneficial for preventing Aβ-induced neuronal cell death associated with AD.