Zhou Zheyi, Dun Linglu, Yang Qian, Tao Jingrui, Yu Peishan, Xu Hong, Zhao Na, Zheng Na, An Hongwei, Yi Ping
Department of Neurology Laboratory, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou 545001, PR China.
Department of Neurology Laboratory, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou 545001, PR China.
Brain Res. 2023 Apr 15;1805:148247. doi: 10.1016/j.brainres.2023.148247. Epub 2023 Jan 17.
Traditional Chinese medicine has emerged as promising targets for ischemic stroke (IS) therapy, yet the mechanism remains elusive. The current study was performed with an aim to investigate the action and mechanism of Tongqiao Huoxue decoction (TQHXD) affecting the neurological impairment secondary to IS based on network pharmacology. Based on network pharmacology and bioinformatics analysis, target genes and pathways involved in the treatment of TQHXD against IS were predicted. Serum containing TQHXD was prepared through blood collection from C57BL/6 mice after intragastric administration of TQHXD. The main results exhibited that Prostaglandin-endoperoxide synthase 2 (PTGS2) exhibited an abundance in IS and enrichment in the NF-kappa B signaling pathway, holding the potential as targets related to TQHXD treatment for IS. TQHXD was found to rescue cell viability, inhibit apoptosis, and alleviate inflammation under oxygen and glucose deprivation and reoxygenation (OGD/R) exposure. Furthermore, our in vivo experiment validated the protective function of TQHXD in ischemic brain damage stimulated by middle cerebral artery occlusion (MCAO). This protective action of TQHXD could be attenuated by overexpressing nuclear factor (NF)-kappa B, which was dependent on PTGS2. Collectively, TQHXD was demonstrated to ameliorate IS-induced neurological impairment by blocking the NF-kappa B signaling pathway and down-regulating PTGS2.
中药已成为缺血性中风(IS)治疗的有前景的靶点,但其机制仍不清楚。本研究旨在基于网络药理学探讨通窍活血汤(TQHXD)对IS继发神经功能缺损的作用及机制。基于网络药理学和生物信息学分析,预测了TQHXD治疗IS所涉及的靶基因和信号通路。在给C57BL/6小鼠灌胃TQHXD后采血制备含TQHXD的血清。主要结果显示,前列腺素内过氧化物合酶2(PTGS2)在IS中表达丰富且在核因子-κB信号通路中富集,有望成为TQHXD治疗IS的相关靶点。研究发现,TQHXD在氧糖剥夺/复氧(OGD/R)条件下可挽救细胞活力、抑制细胞凋亡并减轻炎症。此外,我们的体内实验验证了TQHXD对大脑中动脉闭塞(MCAO)诱导的缺血性脑损伤具有保护作用。TQHXD的这种保护作用可通过过表达核因子(NF)-κB而减弱,且该作用依赖于PTGS2。总的来说,TQHXD可通过阻断核因子-κB信号通路和下调PTGS2来改善IS诱导的神经功能缺损。