Neuroprotective effect of 1-methoxyoctadecan-1-ol from Uncaria sinensis on glutamate-induced hippocampal neuronal cell death

Ethnopharmacological relevance We isolated a single compound, 1-methoxyoctadecan-1-ol (MOD), from dried hooks and stems of Uncaria sinensis , which is used in traditional Korean medicine to provide relief from various nervous related symptoms. Materials and methods Neuroprotective effects of MOD against glutamate-induced oxidative stress in HT22 cells were investigated by analyzing cell viability, lactate dehydrogenase, flow cytometry, reactive oxygen species (ROS) and Western blot assays. Results Exposure to glutamate alone resulted in remarkable hippocampal neuronal cell death; however, pretreatment with MOD resulted in suppression of neuronal death and ROS accumulation in connection with cellular Ca 2+ level after exposure to glutamate. Stimulation by glutamate also caused significant protein level of phosphorylated p38 mitogen-activated protein kinases (MAPK), and dephosphorylated phosphatidylinositol-3 kinase (PI3K), however, pretreatment with MOD resulted in inhibition of these changes in protein level. Treatment with glutamate alone led to suppressed protein level of mature brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (CREB); however, pretreatment with MOD resulted in significant enhancement of this level of protein. Anti-oxidant N-acetyl- L -cysteine and both Ca 2+ inhibitors, BAPTA and EGTA, showed effects similar to those of MOD in all proteins examined, except mature BDNF. Conclusions Our results suggest that MOD mainly exerted neuroprotective effects in suppression of ROS accumulation and up-regulation of mature BDNF in association with p38 MAPK and PI3K signaling in hippocampal neuronal cells.