Licochalcone A减弱了NMDA诱导的神经毒性
Licochalcone A attenuates NMDA-induced neurotoxicity
影响因子:3.20000
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
摘要
这项研究研究了Licochalcone A（LICO-A）的影响，这是一种以其抗炎，抗癌和抗氧化特性而闻名的类黄酮，对NMDA诱导的原代培养的大鼠河马神经元中NMDA诱导的神经毒性。该研究测量了NMDA和LICO-A暴露后的细胞存活，表明以2.5μg/ml的LICO-A可显着提高细胞活力，反对NMDA的有害作用。该研究还通过检查突触后密度95（PSD95）和靶向突触素的成像来分析突触变化，表明LICO-A治疗导致突触点的显着增加，与在NMDA暴露下观察到的减少相反。此外，使用Western Blotting测量了磷酸化的混合谱系激酶域样假酶（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）的水平。结果表明，暴露于NMDA的神经元中P-MLKL和P-RIP3的增加，在LICO-A处理后降低了。还通过免疫染色来评估星形胶质细胞和小胶质细胞的反应，用于神经胶质原纤维酸性蛋白（GFAP），电离钙结合适配器分子1（IBA-1）和肿瘤坏死因子α（TNF-α）。这些标记在NMDA组中表现出较高的表达，通过LICO-A处理大大降低了表达。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，抑制神经元坏死和调节神经胶质激活。因此，对于与NMDA相关的神经毒性相关的疾病，LICO-A作为一种神经保护剂有望。
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.