Abstract. Recent evidence indicates that microglial activation and hippocampal damage may play important roles in neurodegenerative diseases, including Alzheimer's disease. Bambusae Caulis in Taeniam has been used as a folk remedy for the treatment of hypertension and cardiovascular disease in China and Korea. In this study, the mechanism responsible for the neuroprotective and anti-neuroinflammatory effects of Bambusae Caulis in Taeniam ethyl acetate fraction (BCE) was investigated. Heme oxygenase-1 (HO-1) is an inducible enzyme expressed in response to various inflammatory stimuli. Due to its role in the anti-inflammatory signaling pathway, the expression and modulation of HO-1 are important. In this study, the neuroprotective and antineuroinflammatory effects of BCE were examined using the murine microglial BV2 and hippocampal HT22 cells. We demonstrated that the administration of BCE provided neuroprotective effects against glutamate-induced cytotoxicity in HT22 cells through the HO-1 and nuclear erythroid-2 related factor 2 (Nrf-2) signaling pathways. We also reported that BCE inhibited lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and that the presence of selective inhibitors of HO-1 (SnPP) resulted in the inhibition of BCE-mediated anti-inflammatory activity in BV2 microglial cells. BCE was shown to induce HO-1 expression as well as the nuclear translocation of Nrf-2 in both microglial and hippocampal cells. These findings revealed the potential therapeutic mechanisms of BCE in neurodegenerative diseases, suggesting that HO-1 and Nrf-2 signaling may play important roles in the mediation of its neuroprotective and anti-neuroinflammatory effects. IntroductionAlzheimer's disease (AD) is the most common neurodegenerative disease causing adult dementia. The pathological feature of AD is progressive neuronal degeneration in separate areas of the forebrain, including the hippocampus and associated cortices (1). Oxidative stress has also been implicated in the pathophysiological mechanisms underlying AD (2). Thus, the regulation of oxidative stress is important in AD patients.Microglia are the primary immune cells of the brain and play an essential role in the regulation of the immune response triggered by damaged cells (3). Microglial cells are considered 'brain macrophages' because they scavenge dying cells in the brain. However, chronic activation of these cells leads to the production of many pro-inflammatory cytokines and inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 (4). Therefore, the regulation of microglial activation has been regarded as an important therapeutic approach for the treatment of inflammatory neurodegenerative diseases. A number of studies have been conducted using BV2 cells, an immortalized murine microglial cell line. In addition to microglia, the hippocampus, an essential area for memory function, also has an important function pertinent in neurodegenerative diseases. Hippocampal HT22 cells are derived from t...
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