Dicaffeoylquinic acids alleviate memory loss via reduction of oxidative stress in stress-hormone-induced depressive mice. (November 2020) - Lim, Dong Wook
Graphical abstract: Arctium lappa extracts (ALE) alleviated stress hormone-induced depressive behaviors including memory loss by restoring glutamatergic synaptic transmission. diCQAs reduced ROS production by inhibiting monoamine oxidase type A and B activity in primary cultured neurons and astrocytes. In addition, antioxidant effects of diCQAs protect neuronal morphology from stress-hormone-induced effects, followed by recovered stress hormone-induced depression and memory loss in mice. Highlights: Arctium lappa extracts (AL) contains several diCQAs as a bioactive component. diCQAs reduced ROS production by inhibiting monoamine oxidase type A and B activity in primary cultured neurons and astrocytes. diCQAs alleviated stress-hormone-induced depressive behaviors including memory loss by restoring glutamatergic synaptic transmission. Antioxidant effects of diCQAs protect neuronal morphology from stress-hormone induced effects. Abstract: Chronic stress can lead to depression due to elevated levels of stress hormones such as glucocorticoid. This is accompanied by an increase in reactive oxygen species (ROS) levels in the brain, which can cause dendritic spine loss and atrophy in neurons, followed by memory loss. Dicaffeoylquinic acids (diCQAs) are naturally occurring polyphenolic antioxidant compounds in Arctium lappa extracts ( AL ). The effects of natural derivatives of cafferoylqunic acid on stress hormone-induced depressive behavior and their underlying mechanisms are uncertain. In the current study, we showed that diCQAs reduced depressive behaviors including memory loss in corticosterone (CORT) treated mice. The mechanism of anti-depressants of diCQAs is likely through reduction of ROS production by inhibiting the activity of monoamine oxidase (MAO) type A and B in neurons and astrocytes. Among diCQAs, 3, 4- and 3, 5-diCQA significantly inhibited the activity of MAO enzymes followed by the reduction of ROS in neurons and astrocytes and also protected neuronal atrophy and synaptic transmission against stress hormone. These results suggest that 3, 4- and 3, 5-diCQAs effectively reduced depressive symptoms and inhibited ROS production to alleviate memory loss in stress hormone-induced depressive mice and hence, which provide some potential natural antidepressants.