Abstract:
The excessive glutamate-induced oxidative and endoplasmic reticulum (ER) stress is the one of the leading causes of neuronal cell death which associates with many neurodegenerative diseases. Cleistocalyx nervosum var. paniala (CNP) is an indigenous berry fruit found in the North of Thailand. It has many bioactive compounds, especially anthocyanin which has been shown to possess powerful antioxidant properties. The aim of this research was to investigate the neuroprotective effect of CNP extract and its major bioactive compound; cyanidin-3-glucoside (C3G), against ROS-mediated ER stress induced by glutamate in HT22 mouse hippocampal neuronal cells. CNP extract was clarified for its radical scavenging activities, total phenolic and anthocyanin contents. The key anthocyanin-C3G used as a marker to standardize the extract in the study. We found that CNP extract and C3G prevented glutamate-induced apoptosis cell death. For mechanistic approach, glutamate-induced cell death through reactive oxygen species (ROS) -mediated ER stress pathways, indicating by the increase of ROS and ER stress signatures including calpain, caspases-12 and C/EBP homologous proteins (CHOP). CNP extract and C3G suppressed ROS and ER stress in glutamate-treated cells by up-regulating the survival proteins, including extracellular regulated protein kinase (ERK) and nuclear factor E2-related factor2 (Nrf2). Moreover, the gene expressions of endogenous antioxidant enzymes; superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidase (GPx)), and phase II enzymes (glutathione-S-transferases (GSTs)) were significantly increased in CNP extract and C3G treated cells. Taken together, our results provide the information and molecular mechanism of CNP extract and C3G as a promising neuroprotectant and antioxidant via activation of ERK/Nrf2 survival pathway.
