Neuroprotective effects of myristargenol A against glutamate-induced apoptotic HT22 cell death.

Glutamate is an important neurotransmitter in the central nervous system; however, at high concentrations, it causes excitotoxicity and many neurological disorders. Excitotoxicity induces cell death by apoptosis. Thus, factors that can inhibit the apoptotic pathways are a target of drug development for the treatment and prevention of neurodegenerative diseases. Herein, the antioxidative and neuroprotective effects of myristargenol A were examined in glutamate-induced mouse hippocampal neuronal HT22 cells. When the HT22 cells were stressed with glutamate, cell viability decreased to 44.4 ± 5.6% when compared with the case of the control cells (100 ± 4.8%); however, when these cells were treated with myristargenol A (10 μM), the cell viability was increased by 113.6 ± 2.3%. The protective effect of myristargenol A against the apoptosis of glutamate-induced HT22 cells was also confirmed using FITC-annexin V/propidium iodide double staining. In addition, myristargenol A protected the mitochondrial membrane potential (Δ ). Subsequently, the expression levels of proteins in the caspase pathway related with the induction of apoptosis were decreased. Moreover, the expression levels of mitochondrial-related proteins, such as Bcl-2 and Bax, were examined, and it was found that the expression ratio of Bax/Bcl-2 decreased. In addition, myristargenol A inhibited the activity of mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase, for an oxidative stress protection effect but increased the activity of the extracellular signal-regulated kinases 1 and 2 for cell proliferation. These results reveal that myristargenol A possesses a neuroprotective effect against the neuronal cell damage caused by glutamate.