Licocalcone A减轻NMDA诱导的神经毒性

Licochalcone A attenuates NMDA-induced neurotoxicity

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Animal Cells and Systems

影响因子:3.2

分区:生物学3区 / 动物学2区细胞生物学3区

发表日期:2024

作者: Jae Soo Kim, Mi-Hye Kim, Myeung Ju Kim, Hee Jung Kim

DOI: 10.1080/19768354.2024.2389823

摘要

本研究探讨了从甘草根提取的类黄酮化合物Licocalcone A（Lico-A）对NMDA诱导的原代培养大鼠海马神经元中的神经毒性的影响。研究测定了NMDA和Lico-A暴露后细胞存活率，结果显示，浓度为2.5 μg/ml的Lico-A显著改善细胞活性，抵抗NMDA的有害作用。研究还通过检测突触后密度蛋白95（PSD95）及突触素的成像分析了突触变化。结果显示，Lico-A处理组的突触点显著增加，而NMDA处理组则表现为减少。此外，采用Western blot检测了关键的坏死性凋亡调控蛋白磷酸化的混合谱系激酶结构域样假激酶（P-MLKL）和磷酸化的受体相互作用丝氨酸/苏氨酸蛋白激酶3（P-RIP3），结果显示NMDA暴露增加了这两种蛋白的表达，Lico-A处理后则显著降低。此外，还通过免疫染色检测胶质纤维酸性蛋白（GFAP）、离子钙结合伴调蛋白1（IBA-1）和肿瘤坏死因子α（TNF-α）观察星形胶质细胞和微胶质细胞的反应，发现这些标志物在NMDA组中表达升高，Lico-A处理显著减弱了这一反应。这些结果表明，Lico-A具有抗NMDA诱导神经毒性的神经保护作用，可能通过保护突触结构、抑制神经元坏死性凋亡以及调节胶质细胞激活发挥作用。因此，Lico-A有望成为与NMDA相关神经毒性疾病的潜在神经保护剂。

Abstract

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.