本研究探讨甘草查尔酮 A (Lico-A)（一种来自甘草根的黄酮类化合物，以其抗炎、抗癌和抗氧化特性而闻名）对 NMDA 诱导的原代培养大鼠海马神经元神经毒性的影响。该研究测量了暴露于 NMDA 和 Lico-A 后的细胞存活率，结果表明 2.5 μg/ml 的 Lico-A 显着提高了细胞活力，抵消了 NMDA 的有害影响。该研究还通过检查突触后密度 95 (PSD95) 和突触素靶向成像来分析突触变化，结果表明 Lico-A 治疗导致突触斑点显着增加，与 NMDA 暴露下观察到的减少形成鲜明对比。此外，使用蛋白质印迹法测量了关键的坏死性凋亡调节因子磷酸化混合谱系激酶结构域样假激酶 (P-MLKL) 和磷酸化受体相互作用丝氨酸/苏氨酸蛋白激酶 3 (P-RIP3) 的水平。结果显示，暴露于 NMDA 的神经元中 P-MLKL 和 P-RIP3 有所增加，而 Lico-A 处理后则有所减少。还通过胶质纤维酸性蛋白 (GFAP)、离子钙结合接头分子 1 (IBA-1) 和肿瘤坏死因子 α (TNF-α) 的免疫染色评估星形胶质细胞和小胶质细胞的反应。这些标记物在 NMDA 组中表现出较高的表达，但通过 Lico-A 处理后表达显着降低。这些发现表明 Lico-A 对 NMDA 诱导的神经毒性具有神经保护作用，可能有助于突触保存、抑制神经元坏死性凋亡和调节神经胶质活化。因此，Lico-A 显示出作为神经保护剂的前景，用于治疗与 NMDA 相关的神经毒性相关的疾病。© 2024 作者。由 Informa UK Limited 出版，以 Taylor 名义进行交易

This study investigates the effect of Licochalcone A (Lico-A), a flavonoid from licorice roots known for its anti-inflammatory, anti-cancer, and antioxidant properties, on NMDA-induced neurotoxicity in primary cultured rat hippocampal neurons. The study measured cell survival following NMDA and Lico-A exposure, revealing that Lico-A at a 2.5 μg/ml significantly improved cell viability, countering the detrimental effects of NMDA. The study also analyzed synaptic changes by examining both postsynaptic density 95 (PSD95) and synaptophysin-targeted imaging, showing that Lico-A treatment resulted in a significant increase in synaptic puncta, contrasting with the reduction observed under NMDA exposure. Furthermore, levels of phosphorylated mixed lineage kinase domain-like pseudokinase (P-MLKL) and phosphorylated receptor-interacting serine/threonine-protein kinase 3 (P-RIP3), key necroptosis regulators, were measured using Western blotting. The results showed an increase in P-MLKL and P-RIP3 in neurons exposed to NMDA, which was reduced following Lico-A treatment. The response of astrocyte and microglia was also evaluated by immunostaining for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA-1) and tumor necrosis factor alpha (TNF-α). These markers exhibited heightened expression in the NMDA group, which was substantially reduced by Lico-A treatment. These findings suggest that Lico-A has neuroprotective effects against NMDA-induced neurotoxicity, potentially contributing to synaptic preservation, inhibition of neuronal necroptosis, and modulation of glial activation. Therefore, Lico-A shows promise as a neuroprotective agent for conditions associated with NMDA-related neurotoxicity.© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.