Natural sources are very promising materials for the discovery of novel bioactive compounds with diverse pharmacological effects. In recent years, many researchers have focused on natural sources as a means to prevent neuronal cell death in neuropathological conditions. This study focused on identifying neuroprotective compounds and their underlying molecular mechanisms. Procyanidin C1 (PC-1) was isolated from grape seeds and assessed for biological effects against glutamate-induced HT22 cell death. The results showed that PC-1 strongly prevented glutamate-induced HT22 cell death. Moreover, PC-1 was also found to prevent glutamate-induced chromatin condensation and reduce the number of annexin V-positive cells indicating apoptotic cell death. Procyanidin C1 possessed a strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and inhibited glutamate-induced accumulation of intracellular reactive oxygen species and protein carbonylation. Additionally, PC-1 mediated nuclear translocation of nuclear factor erythroid-derived 2-related factor 2 and increased the expression levels of heme oxygenase (HO-1). Inhibition of HO-1 by tin protoporphyrin, a synthetic inhibitor, reduced the protective effect of PC-1. Furthermore, PC-1 also blocked glutamate-induced phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2 and p38, but not JNK. This study is the first experimental report to demonstrate the neuroprotective effects of PC-1 against glutamate-induced cytotoxicity in HT22 cells. Therefore, our results suggest that PC-1, as a potent bioactive compound of grape seeds, can prevent neuronal cell death in neuropathological conditions.
Keywords: MAPK; Nrf2/HO-1 signaling pathway; glutamate; neuroprotective effects; oxidative stress; procyanidin C1.