Department of Histology and Embryology, Basic Medical School of Jining Medical University, Jining, 272001, Shandong, China.
Department of Physiology, Basic Medical School of Jining Medical University, Jining, 272001, Shandong, China.
Mol Cell Biochem. 2021 Feb;476(2):609-617. doi: 10.1007/s11010-020-03930-4. Epub 2020 Oct 19.
The present study screened the effect of Myricitrin on cognitive deficits post-cerebral ischemic stroke and the involved mechanism. The rats were submitted to middle cerebral artery occlusion (MCAO) and were treated with sodium butyrate or Myricitrin (15 and 30 mg/kg) for 28 days. The spatial memory was studied by Morris water maze (MWM). After 4 weeks, the rats were euthanized and hippocampus region was utilized for neurochemical and biochemical changes. The extent of histone acetylation was studied by ELISA. Protein levels were analyzed by Western blot analysis. The mRNA levels were analyzed by polymerase chain reaction (PCR). In silico bioinformatics docking studies were done for target confirmation of Myricitrin. The treatment of Myricitrin showed improved memory in MWM compared to rats treated with vehicle, and the effects of Myricitrin were similar to sodium butyrate-treated rats. At a dose of 30 mg/kg Myricitrin, the histone deacetylase content was decreased, the expression levels of BDNF were increased, the levels of acetylated H3 and H4 along with Syn-I in the hippocampus region were over-expressed compared to control vehicle-treated rats. However, at low dose, i.e., 15 mg/kg Myricitrin failed to show alterations in biochemical as well as neurochemical markers. Docking studies suggested the BDNF and Sun-I as potential target proteins of Myricitrin. The cognitive ameliorating effect of Myricitrin post-cerebral ischemia stroke can be attributed to increased expression of BDNF and Syn-I and modulation of histone acetylation.
本研究筛选了杨梅素对脑缺血后认知障碍的影响及其作用机制。大鼠进行大脑中动脉闭塞（MCAO）后，用丁酸钠或杨梅素（15 和 30mg/kg）处理 28 天。通过 Morris 水迷宫（MWM）研究空间记忆。4 周后，处死大鼠，利用海马区研究神经化学和生化变化。通过 ELISA 研究组蛋白乙酰化程度。通过 Western blot 分析检测蛋白水平。通过聚合酶链反应（PCR）分析 mRNA 水平。进行计算机生物信息学对接研究，以确认杨梅素的作用靶点。与给予载体的大鼠相比，杨梅素治疗组在 MWM 中表现出改善的记忆，且杨梅素的作用与丁酸钠治疗组相似。在 30mg/kg 剂量下，组蛋白去乙酰化酶含量降低，BDNF 表达水平增加，与对照组相比，海马区乙酰化 H3 和 H4 以及 Syn-I 的水平表达上调。然而，在低剂量 15mg/kg 时，杨梅素未能改变生化和神经化学标志物。对接研究表明 BDNF 和 Sun-I 可能是杨梅素的潜在靶蛋白。杨梅素对脑缺血后认知障碍的改善作用可能归因于 BDNF 和 Syn-I 的表达增加以及组蛋白乙酰化的调节。
