Glutamate is the major excitatory neurotransmitter in the central nervous system and is involved in oxidative stress during neurodegeneration. In the present study, casuarinin prevented glutamate-induced HT22 murine hippocampal neuronal cell death by inhibiting intracellular reactive oxygen species (ROS) production. Moreover, casuarinin reduced chromatin condensation and annexin-V-positive cell production induced by glutamate. We also confirmed the underlying protective mechanism of casuarinin against glutamate-induced neurotoxicity. Glutamate markedly increased the phosphorylation of extracellular signal regulated kinase (ERK)-1/2 and p38, which are crucial in oxidative stress-mediated neuronal cell death. Conversely, treatment with casuarinin diminished the phosphorylation of ERK1/2 and P38. In conclusion, the results of this study suggest that casuarinin, obtained from natural products, acts as potent neuroprotective agent by suppressing glutamate-mediated apoptosis through the inhibition of ROS production and activation of the mitogen activated protein kinase (MAPK) pathway. Thus, casuarinin can be a potential therapeutic agent in the treatment of neurodegenerative diseases.

谷氨酸是中枢神经系统中主要的兴奋性神经递质，并在神经变性过程中参与氧化应激。在本研究中，木麻黄素通过抑制细胞内活性氧（ROS）的产生来预防谷氨酸诱导的HT22鼠海马神经元细胞死亡。此外，木麻黄素减少了谷氨酸诱导的染色质凝集和膜联蛋白-V阳性细胞的产生。我们还证实了木麻黄素对谷氨酸诱导的神经毒性的潜在保护机制。谷氨酸显着增加了细胞外信号调节激酶（ERK）-1/2和p38的磷酸化，这在氧化应激介导的神经元细胞死亡中至关重要。相反，用木麻黄素处理可减少ERK1 / 2和P38的磷酸化。综上所述，这项研究的结果表明，从天然产物中获得的木麻黄素可通过抑制ROS的产生和丝裂原活化蛋白激酶（MAPK）途径的活化来抑制谷氨酸介导的细胞凋亡，从而起到有效的神经保护作用。因此，木麻黄素可以是治疗神经退行性疾病的潜在治疗剂。