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).
Keywords: Apoptosis; Cornuside; OGD/R; Oxidative stress; P53; p38/JNK MAPK.
Copyright © 2023 Elsevier B.V. All rights reserved.