Oxidative stress-mediated memory impairment during aging and its therapeutic intervention by natural bioactive compounds

Abstract

Aging and associated neurodegenerative diseases are accompanied by the decline of several brain functions including cognitive abilities. Progressive deleterious changes at biochemical and physiological levels lead to the generation of oxidative stress, accumulation of protein aggregates, mitochondrial dysfunctions, loss of synaptic connections, and ultimately neurodegeneration and cognitive decline during aging. Oxidative stress that arises due to an imbalance between the rates of production and elimination of free radicles is the key factor for age-associated neurodegeneration and cognitive decline. Due to high energy demand, the brain is more susceptible to free radicals-mediated damages as they oxidize lipids, proteins, and nucleic acids, thereby causing an imbalance in the homeostasis of the aging brain. Animal, as well as human subject studies, showed that with almost no or few side effects, dietary interventions and plant-derived bioactive compounds could be beneficial to recovering the memory or delaying the onset of memory impairment. As the plant-derived bioactive compounds have antioxidative properties, several of them were used to recover the oxidative stress-mediated changes in the aging brain. In the present article, we review different aspects of oxidative stress-mediated cognitive change during aging and its therapeutic intervention by natural bioactive compounds.

Keywords: aging; bioactive compounds; memory; neurodegeneration; oxidative stress.

FIGURE 1

Chemical structure of selected plant-derived bioactive compounds.

FIGURE 2

Schematic diagram representing the antioxidant properties of plant-derived bioactive compounds in the recovery of oxidative stress-mediated changes in the aging brain. Age-associated cellular and biochemical changes such as mitochondrial dysfunction, and decline of antioxidant enzyme systems lead to the generation of excessive reactive free radicals. These free radicals cause changes in the biological macromolecules (lipid peroxidation, oxidation of protein, and nucleic acid) and thus facilitate cellular or mitochondrial membrane damage, modified protein accumulation, double-stranded DNA break, and epigenetic modifications. These oxidative stress-mediated damages ultimately lead to neurodegeneration and decline of cognitive functions during aging or associated neurodegenerative diseases. Supplementation of plant-derived bioactive compounds ameliorates the age-associated neurodegeneration and cognitive dysfunctions by increasing the activities of antioxidant enzymes and decreasing the oxidative stress-induced damages to biological macromolecules.