Neuroprotective and Antioxidant Effect of Cheongwisan Against Glutamate-induced Excitotoxicity

Oxidative stress contributes to neuronal damage and neurodegenerative disease as Alzheimer’s disease (AD). While glutamate, a key neurotransmitter in the central nervous system, is fundamental to neuronal viability and normal brain function, its excessive accumulation leads to oxidative stress. In this study, we investigated the effect of Cheongwisan (CWS), as Korean medicine consist in 5 nature herbs, on glutamate-induced injury in HT22 cells and explored the underlying mechanism involved. Our results show that CWS significantly reduced neuronal cell death and apoptotic marker. Also, CWS has antioxidant effect, reducing reactive oxygen species (ROS) level and increasing antioxidant molecules as heme oxygenase-1 (HO1), NAD(P)H: quinone oxidoreductase 1 (NQO1). Western blot analysis revealed that CWS upregulated brain-derived neurotrophic factor (BDNF) and promoted the extracellular signal-regulated kinase (ERK), and cAMP response element binding protein (CREB), which were downregulated by glutamate. Furthermore, CWS promoted the translocation of nuclear factor erythroid 2-related factor 2 (NRF2) into the nuclear. Thus, CWS may protect hippocampal cells against glutamate-induced oxidative stress by acti- vating the BDNF/ERK/CREB and ERK/NRF2 signaling pathways, suggesting its therapeutic potential for AD.