Department of Neurology, Ninth Hospital of Xi'an, Xi'an, Shaanxi, China.
Department of Neurology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong, China.
J Biochem Mol Toxicol. 2021 Feb;35(2):e22634. doi: 10.1002/jbt.22634. Epub 2020 Sep 29.
Chrysin is the major bioactive compound of blue passionflower, an important medicinal plant used in traditional herbal formulations since ancient times. In the present study, we report that chrysin nanoparticles (chrysin NPs) protect Wistar rats against kindling-induced epilepsy. Nanoparticles of sizes less than 150 nm with a spherical shape were prepared using poly(d,l-lactic-co-glycolic acid) and polyvinyl alcohol, respectively, as polymer and stabilizer. Rats were injected with subconvulsive doses of pentylenetetrazole (PTZ) (35 mg/kg, intraperitoneal) every second day, with 22 injections in total, and on the same days, they received protective doses of the chrysin NPs (5 and 10 µg/mL, PO), respectively, 45 min before each PTZ injection. After the last PTZ injection, an average of thirteen seizure scores was recorded. Animals were killed by decapitation 24 h after a seizure. The cortex and hippocampus were removed and stored in liquid nitrogen for determining oxidative stress terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, histopathology, and reverse transcription-polymerase chain reaction for messenger RNA expression. The result showed chrysin NPs treatment has counteracted oxidative stress, reduced neuronal apoptosis, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1. In conclusion, our findings demonstrate that the neuroprotective effect of chrysin NPs against kindling-induced epilepsy might be escorted by the alleviation of oxidative stress through the Nrf2/antioxidant response element/HO-1 pathway signal pathway.
白杨素是蓝叶西番莲的主要生物活性化合物，蓝叶西番莲是一种自古以来就用于传统草药配方的重要药用植物。在本研究中，我们报告白杨素纳米粒子（chrysin NPs）可保护 Wistar 大鼠免受点燃诱导的癫痫发作。使用聚（D，L-丙交酯-共-乙交酯）和聚乙烯醇分别作为聚合物和稳定剂制备粒径小于 150nm 的球形纳米粒子。大鼠每隔一天腹腔注射亚惊厥剂量的戊四氮（PTZ）（35mg/kg），共 22 次，并且在同一天，它们分别接受保护剂量的白杨素 NPs（5 和 10μg/mL，PO），在每次 PTZ 注射前 45 分钟。在最后一次 PTZ 注射后，记录平均 13 次发作评分。动物在癫痫发作后 24 小时通过断头处死。取出大脑皮质和海马并储存在液氮中，用于测定氧化应激末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定、组织病理学和信使 RNA 表达的逆转录聚合酶链反应。结果表明，白杨素 NPs 治疗可对抗氧化应激，减少神经元凋亡，并上调核因子红细胞 2 相关因子 2（Nrf2）、血红素加氧酶-1（HO-1）和 NAD（P）H 醌氧化还原酶 1。总之，我们的研究结果表明，白杨素 NPs 对点燃诱导的癫痫发作的神经保护作用可能通过 Nrf2/抗氧化反应元件/HO-1 通路信号通路缓解氧化应激来实现。
