Mechanisms of Anti-Glutamate Neurotoxicity of Botanicals and their Chemical Constituents

In many countries, including Asian countries such as Japan, Singapore and Thailand, aging populations have been increasing, thus promoting a high risk for ageassociated chronic diseases. One of the devastating chronic diseases in people with old age known to greatly impact the patients’ quality of life is a group of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. It has been evident that neurotoxicity is a significant risk of neurodegenerative disorders. One of the crucial contributing factors leading to neurotoxicity in humans is glutamate, the excitatory neurotransmitter. If it is accumulated in the brain, this neurotransmitter can result in neurotoxicity via either glutamate-dependent pathway or glutamateindependent pathway. Glutamate neurotoxicity (GNT) is characterized by rising damage of cell components leading to cell death. In the death process due to oxidative stress, reactive oxygen species (ROS) are generated, thus impairing a vast array of cellular functions in many organelles such as mitochondria and endoplasmic reticulum. GNT has been clearly observed in the brain tissue because of the accumulation of glutamate, not only from the endogenous source, but also the exogenous source such as monosodium glutamate. Fortunately, numerous plant extracts and their chemical constituents, particularly the ones with high anti-oxidant activity, have been found to exhibit anti-GNT in both vitro and in vivo models. Herein, mechanisms of anti-GNT of botanicals and their chemical constituents are presented and discussed in detail. Their anti-GNT mechanisms elucidated could shed light on the discovery and application of neutraceuticals, and the cell defense mechanisms of natural neuroprotectants could certainly be beneficial to improve both healthspan and lifespan in humans.

Keywords: Glutamate neurotoxicity, Natural products, Neuroprotectants, Neutraceuticals, Reactive oxygen species.