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. 2015 Dec;18(12):1333-9.
doi: 10.1089/jmf.2014.3412. Epub 2015 Jul 15.

Valerenic Acid Protects Against Physical and Psychological Stress by Reducing the Turnover of Serotonin and Norepinephrine in Mouse Hippocampus-Amygdala Region

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Valerenic Acid Protects Against Physical and Psychological Stress by Reducing the Turnover of Serotonin and Norepinephrine in Mouse Hippocampus-Amygdala Region

Hyo Young Jung et al. J Med Food. .
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Abstract

In a previous study, we demonstrated that a Valeriana officinalis extract could attenuate increases in serum corticosterone levels in a mouse model of physical and psychological stress. In addition, our results showed that the extract could modulate serotonin (5-HT) and norepinephrine (NE) turnover in the hippocampus and amygdala region. In this study, we intended to investigate the effects of valerenic acid (VA), the main component of V. officinalis extract, on corticosterone levels in serum in normal mice and monoamine turnover in hippocampus-amygdala homogenates in a mouse model of physical and psychological stress. To determine the minimum dose of VA for antianxiety effect, eight-week-old ICR mice were orally administered VA (0.2, 0.5, and 1.0 mg/kg/0.3 mL) once daily for 3 weeks to probe for immobility time and serum corticosterone levels. At a VA dose of 0.5 and 1.0 mg/kg, animals showed a decrease in the duration of immobility time and serum corticosterone levels. To confirm the antianxiety effect of VA, eight-week-old ICR mice received VA at a dose of 0.5 mg/kg, orally, once daily for 3 weeks, before being subjected to physical or psychological stress for 3 days, in a specially designed communication box, followed by estimation of levels of monoamines and their metabolites in the hippocampus-amygdala region. In conclusion, VA administration at 0.5 mg/kg can mitigate the physical and psychological stress response by decreasing the turnover of 5-HT to 5-hydroxyindoleacetic acid and NE to 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in the hippocampus and amygdala.

Keywords: norepinephrine; physical stress; psychological stress; serotonin; serum corticosterone; valerenic acid.

Figures

<b>FIG. 1.</b>
FIG. 1.
Experimental protocol and floor plan scheme of the communication box used in the study.
<b>FIG. 2.</b>
FIG. 2.
Effects of valerenic acid (VA) on immobilized activity in the forced swimming test and serum corticosterone level of vehicle-, 0.2, 0.5, and 1.0 mg/kg VA-treated group (n=7 per group; aP<.05 indicating a significant difference as compared to the vehicle group). Error bars indicate standard error of mean (SEM).
<b>FIG. 3.</b>
FIG. 3.
Effect of VA on levels of norepinephrine (NE), its metabolite (3-methoxy-4-hydroxyphenylethyleneglycol sulfate [MHPG-SO4]) and ratio (MHPG-SO4/NE) in the control, vehicle control followed by physical stress (V-PS), VA-treatment followed by PS (VA-PS), vehicle control followed by PCS (V-PCS), and VA-treatment followed by PCS (VA-PCS) (n=8 per group; aP<.05, indicating a significant difference as compared to the control group; bP<.05, significantly different from the V-PS vs. VA-PS or V-PCS vs. VA-PCS group). Error bars indicate SEM.
<b>FIG. 4.</b>
FIG. 4.
Effect of VA on levels of serotonin (5-hydroxytryptamine [5-HT]), its metabolite (5-hydroxyindoleacetic acid [5-HIAA]), and ratio (5-HIAA/5-HT) in the control, vehicle control followed by physical stress (V-PS), VA-treatment followed by PS (VA-PS), vehicle control followed by PCS (V-PCS), and VA-treatment followed by PCS (VA-PCS) (n=8 per group; aP<.05, indicating a significant difference as compared to the control group; bP<.05, significantly different from the V-PS vs. VA-PS or V-PCS vs. VA-PCS group). Error bars indicate SEM.

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