Abstract
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.
Highlights
The central nervous system is especially vulnerable to oxidative stress because of its high content of polyunsaturated fatty acid, high demand for oxygen consumption, and limited antioxidative systems [1]
We recently reported that ellagitannins from natural plant, such as casuarinin and chebulinic acid, strongly prevented glutamate-induced HT22 cell death neuroprotective effects [20,21]
These results suggest that Procyanidin C1 (PC-1) from grape seeds could be a valuable compound for exhibiting neuroprotective effects
Summary
The central nervous system is especially vulnerable to oxidative stress because of its high content of polyunsaturated fatty acid, high demand for oxygen consumption, and limited antioxidative systems [1]. Oxidative stress plays a crucial role in neuronal cell death, contributing to neurological diseases including Parkinson’s disease, Alzheimer’s disease, and strokes [2]. It is well known that excessive oxidative stress can cause DNA and protein oxidation and lipid peroxidation and promotes neuronal cell death [3,4]. Oxidative stress can enhance intracellular Ca2+ concentration [5], and activate neuro-inflammatory reactions and apoptotic pathways [6]. A previous study has suggested that excessive levels of oxidative stress and the disturbance of the antioxidant defense enzyme system in the brain constitute a pathological biomarker for neurological diseases [7]. The prevention of oxidative stress could be a potential therapeutic target for neurological diseases, and many researchers have contributed to the identification of agents which possess antioxidant activity or enhance antioxidant defense enzymes
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