Department of Pediatrics, The Second Hospital of Shandong University, Jinan, 250012, China.
Department of Ophthalmology, The Second People's Hospital of Jinan City, Jinan, 250000, China.
Inflammopharmacology. 2019 Dec;27(6):1143-1153. doi: 10.1007/s10787-019-00592-7. Epub 2019 Apr 29.
Epileptogenesis is a complex pathological process that occurs after an initial brain injury and involves a series of molecular events. Isoliquiritigenin (ISL), a flavonoid in licorice, is reported to have anti-inflammatory and antioxidant effects in various experimental models, but its specific roles and molecular mechanisms in the epileptogenic process following kainic acid (KA) treatment remain unclear. The purpose of this study was to explore the effects of ISL pretreatment in KA-induced epileptic rats and the underlying mechanisms. Our findings show that ISL pretreatment significantly attenuated the KA-induced expression of ionized calcium-binding adapter molecule 1 (IBα1)-labeled microglia (F = 97.29, p < 0.01, ηp = 0.94) and glial fibrillary acidic protein (GFAP)-positive astrocytes (F = 72.48, p < 0.01, ηp = 0.92), and the release of inflammatory mediators, such as TNF-α (F = 133.14, p < 0.01, ηp = 0.95), IL-1β, and C-C motif chemokine ligand 3 (CCL3). ISL pretreatment given before KA also significantly prevented apoptotic neuronal injury by upregulating the activities of superoxide dismutase and glutathione peroxidase. It also significantly suppressed the protein levels of Toll-like receptor 4 (TLR4) (F = 63.23, p < 0.01, ηp = 0.91) and its downstream molecules, myeloid differentiation primary response 88 (MYD88), phosphorylated (p-)IκBα, and p-NF-κB. Blocking TLR4/MYD88 signaling also attenuated KA-induced neuroinflammation and neuronal damage in the hippocampus. Overall, our study demonstrates that ISL pretreatment plays neuroprotective and anti-inflammatory roles in KA-induced epileptogenesis, which may be mediated by the TLR4/MYD88 signaling pathway.
癫痫发生是一种复杂的病理过程，发生在初始脑损伤之后，涉及一系列分子事件。甘草中的异甘草素（ISL）在各种实验模型中具有抗炎和抗氧化作用，但它在红藻氨酸（KA）处理后癫痫发生过程中的具体作用和分子机制尚不清楚。本研究旨在探讨 ISL 预处理对 KA 诱导的癫痫大鼠的作用及其机制。我们的研究结果表明，ISL 预处理显著减轻了 KA 诱导的离子钙结合接头分子 1（IBα1）标记的小胶质细胞（F=97.29，p<0.01，ηp=0.94）和神经胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞（F=72.48，p<0.01，ηp=0.92）的表达，以及炎症介质如肿瘤坏死因子-α（TNF-α）（F=133.14，p<0.01，ηp=0.95）、白细胞介素-1β和 C-C 基序趋化因子配体 3（CCL3）的释放。KA 前给予 ISL 预处理还通过上调超氧化物歧化酶和谷胱甘肽过氧化物酶的活性，显著预防了凋亡性神经元损伤。它还显著抑制了 Toll 样受体 4（TLR4）（F=63.23，p<0.01，ηp=0.91）及其下游分子髓样分化初级反应 88（MYD88）、磷酸化（p-）IκBα和 p-NF-κB 的蛋白水平。阻断 TLR4/MYD88 信号通路也减轻了 KA 诱导的海马神经炎症和神经元损伤。总之，我们的研究表明，ISL 预处理在 KA 诱导的癫痫发生中发挥神经保护和抗炎作用，这可能是通过 TLR4/MYD88 信号通路介导的。
