Abstract
Oxidative stress is believed to be one of the main causes of neurodegenerative diseases such as Alzheimer’s disease (AD). The pathogenesis of AD is still not elucidated clearly but oxidative stress is one of the key hypotheses. Here, we found that artemisinin, an anti-malarial Chinese medicine, possesses neuroprotective effects. However, the antioxidative effects of artemisinin remain to be explored. In this study, we found that artemisinin rescued SH-SY5Y and hippocampal neuronal cells from hydrogen peroxide (H2O2)-induced cell death at clinically relevant doses in a concentration-dependent manner. Further studies showed that artemisinin significantly restored the nuclear morphology, improved the abnormal changes in intracellular reactive oxygen species (ROS), reduced the mitochondrial membrane potential, and caspase-3 activation, thereby attenuating apoptosis. Artemisinin also stimulated the phosphorylation of the adenosine monophosphate -activated protein kinase (AMPK) pathway in SH-SY5Y cells in a time- and concentration-dependent manner. Inhibition of the AMPK pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells. Similar results were obtained in primary cultured hippocampal neurons. Cumulatively, these results indicated that artemisinin protected neuronal cells from oxidative damage, at least in part through the activation of AMPK. Our findings support the role of artemisinin as a potential therapeutic agent for neurodegenerative diseases.
Highlights
Neuronal damage caused by oxidative stress is one of the major causes of neurodegenerative diseases such as Alzheimer’s disease (AD) [1,2,3]
SH-SY5Y cells were incubated with different concentrations of artemisinin or H2O2 for 24 h and the cell viability was determined by MTT assay
Compared with the control group, H2O2 caused significant cytotoxicity in SH-SY5Y cells 600 μM onwards (Figure 1C), and 600 μM H2O2 concentration was used in further experiments
Summary
Neuronal damage caused by oxidative stress (mainly reactive oxygen species) is one of the major causes of neurodegenerative diseases such as Alzheimer’s disease (AD) [1,2,3]. Decreased mitochondrial membrane potential is a marker of early cell apoptosis and is closely related to cellular oxidative damage and apoptosis.The production of ROS occurs mainly in mitochondria and it accumulates during aging becoming a major cause of cellular damage. The effects of age associated decline in AMPK activity on mitochondrial dysfunction and age related oxidative damage have been verified previously [23]. The AMPK signaling pathway plays an important role in systemic energy balance and metabolism and regulation of age-related diseases [11,25,26]. We delineated the role of the AMPK signaling pathway in the protective effect of artemisinin All of these may provide interesting insights into the potential applications of artemisinin in future AD research
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