Guan Yue, Cao Yan-Li, Liu Jia-Wei, Liu Lan-Tao, Zheng Yu-Jia, Ma Xue-Fei, Zhai Feng-Guo
Department of Clinical Medicine, Heilongjiang Nursing College, Harbin, 150001, Heilongjiang Province, China.
School of Pharmacy, Mudanjiang Medical University, Mudanjiang, 157011, Heilongjiang Province, China.
Exp Cell Res. 2023 May 1;426(1):113552. doi: 10.1016/j.yexcr.2023.113552. Epub 2023 Mar 11.
It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.
人们认识到，脑缺血/再灌注（I/R）损伤会引发小胶质细胞的炎症激活，并加剧小胶质细胞驱动的神经元损伤。我们之前的研究表明，人参皂苷Rg1对大脑中动脉闭塞（MCAO）大鼠的局灶性脑I/R损伤具有显著的保护作用。然而，其机制仍需进一步阐明。在此，我们首次报道人参皂苷Rg1在I/R条件下通过抑制Toll样受体4（TLR4）蛋白有效地抑制了脑小胶质细胞的炎症激活。体内实验表明，给予人参皂苷Rg1可显著改善MCAO大鼠的认知功能，体外实验数据表明，人参皂苷Rg1通过梯度依赖性地抑制在氧糖剥夺/复氧（OGD/R）条件下共培养的小胶质细胞中的炎症反应，显著减轻神经元损伤。机制研究表明，人参皂苷Rg1的作用取决于对小胶质细胞中TLR4/MyD88/NF-κB和TLR4/TRIF/IRF-3信号通路的抑制。总之，我们的研究表明，人参皂苷Rg1通过靶向小胶质细胞中的TLR4蛋白，在减轻脑I/R损伤方面具有巨大的应用潜力。
