Department of Rehabilitation Medicine, Binzhou Medical University, Yantai 264003, PR China; Department of Rehabilitation Medicine, Shengli Oilfield Central Hospital, Dongying 257097, PR China.
Department of Rehabilitation Medicine, Binzhou Medical University, Yantai 264003, PR China.
Brain Res. 2023 Dec 15;1821:148585. doi: 10.1016/j.brainres.2023.148585. Epub 2023 Sep 16.
Apoptosis induced by oxygen-glucose deprivation/reperfusion (OGD/R) injury is the main cause of neuronal damage. Cornuside, a small-molecule cyclic enol ether terpene glycoside extracted from the dried fruit of mature Cornus officinalis Sieb. et Zucc., has vigorous anti-apoptotic and antioxidant effects. Previous studies have shown that Cornuside can reduce apoptosis and improve mitochondrial energy metabolism in cortical neurons of rats by inhibiting caspase-3 and calcium release. In this study, we treated SH-SY5Y cells with OGD/R to simulated ischemia/reperfusion (I/R) injury. Using high-throughput transcriptome sequencing, differentially expressed genes were analyzed in the OGD/R group versus the OGD/R + Cornuside (10 μmol/L) group to explore the neuroprotective mechanisms of Cornuside. The differentially expressed genes were mainly enriched in apoptosis signaling pathway, cell cycle, DNA damage and repair, and p38/JNK MAPK and p53 signaling pathways. The results showed that OGD/R significantly reduced the survival of SH-SY5Y cells, induced apoptosis, disrupted the nucleus, promoted the release of ROS, and led to cell cycle arrest. Cornuside reversed OGD/R-induced damage. By upregulating MAPK8IP1 and downregulating MAPK14, TP53INP1, and signaling pathway-related proteins (p-p38, p-JNK, and p-p53), Cornuside ameliorated cell damage induced by p38/JNK MAPK and p53 signaling pathways. Cornuside also downregulated apoptosis regulatory proteins (Bax, Bcl-2, caspase-3, caspase-9, and cytochrome c) and cell cycle regulatory proteins (cyclin B1, cyclin E, and p21).
氧葡萄糖剥夺/再灌注（OGD/R）损伤诱导的细胞凋亡是神经元损伤的主要原因。从山茱萸科山茱萸属植物山茱萸的干燥成熟果肉中提取的小分子环烯醚萜苷 Cornuside 具有很强的抗凋亡和抗氧化作用。先前的研究表明，Cornuside 通过抑制半胱天冬酶-3 和钙释放，减少皮质神经元中的细胞凋亡并改善线粒体能量代谢。在本研究中，我们用 OGD/R 处理 SH-SY5Y 细胞来模拟缺血/再灌注（I/R）损伤。通过高通量转录组测序，分析 OGD/R 组与 OGD/R+Cornuside（10μmol/L）组之间差异表达的基因，以探讨 Cornuside 的神经保护机制。差异表达的基因主要富集在凋亡信号通路、细胞周期、DNA 损伤和修复以及 p38/JNK MAPK 和 p53 信号通路。结果表明，OGD/R 显著降低了 SH-SY5Y 细胞的存活率，诱导细胞凋亡，破坏细胞核，促进 ROS 的释放，并导致细胞周期停滞。Cornuside 逆转了 OGD/R 诱导的损伤。通过上调 MAPK8IP1 和下调 MAPK14、TP53INP1 和信号通路相关蛋白（p-p38、p-JNK 和 p-p53），Cornuside 改善了 p38/JNK MAPK 和 p53 信号通路诱导的细胞损伤。Cornuside 还下调了凋亡调节蛋白（Bax、Bcl-2、caspase-3、caspase-9 和细胞色素 c）和细胞周期调节蛋白（cyclin B1、cyclin E 和 p21）。
