Glutamate-induced excitotoxicity and oxidative stress is a major causative factor in neuronal cell death in acute brain injuries and chronic neurodegenerative diseases. The prevention of oxidative stress is a potential therapeutic strategy. Therefore, in the present study, we aimed to examine a potential therapeutic agent and its protective mechanism against glutamate-mediated cell death. We first found that chebulinic acid isolated from extracts of the fruit of Terminalia chebula prevented glutamate-induced HT22 cell death. Chebulinic acid significantly reduced intracellular reactive oxygen species (ROS) production and Ca²⁺ influx induced by glutamate. We further demonstrated that chebulinic acid significantly decreased the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, and p38, as well as inhibiting pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 protein expression. Moreover, we demonstrated that chebulinic acid significantly reduced the apoptosis induced by glutamate in HT22 cells. In conclusion, our results in this study suggest that chebulinic acid is a potent protectant against glutamate-induced neuronal cell death via inhibiting ROS production, Ca²⁺ influx, and phosphorylation of MAPKs, as well as reducing the ratio of Bax to Bcl-2, which contribute to oxidative stress-mediated neuronal cell death.

谷氨酸引起的兴奋性毒性和氧化应激是急性脑损伤和慢性神经退行性疾病中神经元细胞死亡的主要诱因。预防氧化应激是一种潜在的治疗策略。因此，在本研究中，我们旨在研究潜在的治疗剂及其针对谷氨酸介导的细胞死亡的保护机制。我们首先发现，从Terminalia chebula果实提取物中分离出的次膦酸可防止谷氨酸诱导的HT22细胞死亡。叶酸可显着降低细胞内活性氧（ROS）的产生和Ca ²⁺谷氨酸引起的内流。我们进一步证明，次膦酸可显着降低包括ERK1 / 2，JNK和p38在内的丝裂原活化蛋白激酶（MAPK）的磷酸化，以及抑制促凋亡Bax和增加抗凋亡Bcl-2蛋白表达。此外，我们证明了次膦酸可显着减少谷氨酸诱导的HT22细胞凋亡。总之，我们在这项研究中的结果表明，次膦酸是一种有效的保护剂，可通过抑制ROS的产生，Ca ^2+的流入和MAPK的磷酸化以及降低Bax与Bcl-2的比例来对抗谷氨酸诱导的神经元细胞死亡。，这有助于氧化应激介导的神经元细胞死亡。