Currently, the excessive activation of N-methyl-D-aspartate receptors (NMDARs) is considered to be a crucial mechanism of brain injury. Lycium barbarum A (LyA) is a dimer of phenol amides isolated from the fruit of Lycium barbarum. Our previous studies have shown that LyA has potential antioxidant activity. This study aimed to explore the neuroprotective effect of LyA and its potential mechanism. Firstly, the molecular docking was used to preliminarily explore the potential function of LyA to block NMDAR. Then, the ability of LyA was further verified by NMDA-induced human neuroblastoma SH-SY5Y cells in vivo. Treatment with LyA significantly attenuated NMDA-induced neuronal insults by increasing cell viability, reducing lactate dehydrogenase (LDH) release, and increasing cell survival. Meanwhile, LyA significantly reversed the increase in intracellular calcium and in ROS production induced by NMDA. Finally, the western blot indicated that LyA could suppress the Ca²⁺ influx and increase the p-NR2B, p-CaMKII, p-JNK, and p-p38 level induced by NMDA. These above findings provide evidence that LyA protect against brain injury, and restraining NMDARs and suppressing mitochondrial oxidative stress and inhibiting cell apoptosis may be involved in the protective mechanism.

目前，N-甲基-D-天冬氨酸受体（NMDARs）的过度激活被认为是脑损伤的关键机制。Lycium barbarum A (LyA) 是从枸杞果实中分离的酚酰胺二聚体. 我们之前的研究表明，LyA 具有潜在的抗氧化活性。本研究旨在探讨 LyA 的神经保护作用及其潜在机制。首先，通过分子对接初步探索LyA阻断NMDAR的潜在功能。然后，通过 NMDA 诱导的人神经母细胞瘤 SH-SY5Y 细胞在体内进一步验证了 LyA 的能力。LyA 治疗通过增加细胞活力、减少乳酸脱氢酶 (LDH) 释放和增加细胞存活率来显着减轻 NMDA 诱导的神经元损伤。同时，LyA 显着逆转了 NMDA 诱导的细胞内钙和 ROS 产生的增加。最后，蛋白质印迹表明 LyA 可以抑制 Ca ²⁺NMDA 诱导的 p-NR2B、p-CaMKII、p-JNK 和 p-p38 水平流入并增加。上述发现提供了LyA对脑损伤的保护作用的证据，抑制NMDARs、抑制线粒体氧化应激和抑制细胞凋亡可能参与了保护机制。