Department of Rehabilitation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Department of Neurology, The Fifth Hospital of Jinan, Jinan, China.
J Pharm Pharmacol. 2020 Sep;72(9):1176-1185. doi: 10.1111/jphp.13293. Epub 2020 May 21.
Curcumin presents some therapeutic effects including anti-cancer and anti-inflammation. Herein, we centred on the functional role of curcumin in cerebral ischaemia injury and its potential molecular mechanisms.
Microarray analysis was used for excavating crucial genes in cerebral ischaemia. PC12 cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) to imitate cerebral ischaemia/reperfusion (I/R) injury in vitro. Cell viability and apoptosis abilities were evaluated by Cell Counting Kit-8 and flow cytometry assays. qRT-PCR, Western blot and enzyme-linked immunosorbent assays were performed to assess the concentrations of related genes.
By enquiring GEO dataset, C-C motif chemokine ligand 3 (CCL3) was profoundly upregulated in cerebral I/R injury model. And CCL3 was found to be highly expressed in PC12 cells suffered from OGD/R. Moreover, we found that CCL3 was a potential target of curcumin in cerebral I/R injury. More importantly, the following experiments illustrated that curcumin inhibited the expression of CCL3 in OGD/R model and reduced cell apoptosis and inflammation. Moreover, high expression levels of TLR4, MyD88, p-NF-κB P65, p-P38 MAPK and p-IκBα in OGD/R model were inhibited by curcumin.
Our study manifested that curcumin might be a meritorious drug for the treatment of cerebral ischaemia by acting on CCL3.
姜黄素具有抗癌和抗炎等多种治疗作用。本文主要探讨了姜黄素在脑缺血损伤中的功能作用及其潜在的分子机制。
利用基因芯片分析挖掘脑缺血相关的关键基因。体外采用氧葡萄糖剥夺/复氧(OGD/R)模拟脑缺血/再灌注(I/R)损伤,应用细胞计数试剂盒-8(CCK-8)和流式细胞术检测细胞活力和凋亡情况。实时定量聚合酶链式反应(qRT-PCR)、Western blot 和酶联免疫吸附试验(ELISA)检测相关基因的浓度。
通过查询 GEO 数据集,发现趋化因子 C-C 基元配体 3(CCL3)在脑 I/R 损伤模型中显著上调。并且在经历 OGD/R 的 PC12 细胞中发现 CCL3 高表达。此外,我们发现 CCL3 是姜黄素在脑 I/R 损伤中的潜在靶点。更重要的是,以下实验表明姜黄素抑制 OGD/R 模型中 CCL3 的表达,减少细胞凋亡和炎症。此外,OGD/R 模型中 TLR4、MyD88、p-NF-κB P65、p-P38 MAPK 和 p-IκBα 的高表达水平也被姜黄素抑制。
本研究表明,姜黄素可能通过作用于 CCL3 成为治疗脑缺血的一种有效药物。