Serum Metabonomic Study on the Antidepressant-like Effects of Ellagic Acid in a Chronic Unpredictable Mild Stress-Induced Mouse Model

• DOI: 10.1021/acs.jafc.0c02895
• Publication Date: 2020-08-06T00:47:13Z
• Authors: Xiaoxia Huang; Wu Li; Bangyan You; Wanpei Tang; Tingsheng Gan; Chao Feng; Congfa Li; Ruili Yang
• Keywords: Male; Serum; 0301 basic medicine; Serotonin; 0303 health sciences; Behavior, Animal; Depression; Brain-Derived Neurotrophic Factor; Hippocampus; Antidepressive Agents; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Ellagic Acid; Animals; Humans; Metabolomics; Stress, Psychological

As a polyphenol, ellagic acid (EA) has shown potential antidepressant activity. In this study, the effects and serum metabolomic analysis of EA against depression were investigated using a chronic unpredictable mild stress-induced (CUMS) model. EA (20 or 100 mg/kg body weight) significantly ameliorated the CUMS-induced depression-like behaviors, including reduced body weight, decreased sucrose preference, and increased immobility time in both the tail suspension test and the forced swimming test. Furthermore, EA attenuated the CUMS-induced hippocampal damage and significantly increased the brain-derived neurotrophic factor (BDNF) and the serotonin (5-HT) levels as well as suppressed the inflammatory response. The metabolomics analysis showed that the disturbance of glycerophospholipid (phosphatidylethanolamine and phosphatidylinositol), amino acid (l-arginine and N-stearoyl serine), and purine (uric acid) metabolism induced by CUMS was attenuated by the EA treatment. Furthermore, the correlation analysis indicated that the metabolite changes were strongly correlated with behavioral disorders, BDNF, 5-HT, and inflammatory cytokines levels. This study provided new insights for the antidepressant effects of EA and suggests that EA may be a potential nutraceutical for improving the management of depression.