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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.

Procyanidin A2 (PCA2) has been shown to improve lipid metabolism. However, it remains to know whether it can play a role in preventing atherosclerosis (AS) through gut microbiota. This study examined the effect of PCA2 on high fat diet (HFD)-induced AS in ApoE −/− mice with an intact and antibiotic-depleted microbiota. PCA2 administration for 12 weeks attenuated HFD-induced AS in ApoE −/− mice, evidenced by obviously alleviating the histological abnormalities of the aorta, lipid accumulation, oxidative stress, and inflammation, which were accompanied by downregulating the expression of vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 and upregulating peroxisome proliferator-activated receptor gamma, cholesterol 7 alpha-hydroxylase, and ATP-binding cassette transporter A1. Moreover, PCA2 treatment reshaped the gut microbiota imbalance caused by HFD, especially reducing the ratio of Firmicutes/Bacteroidetes and increasing the abundance of Verrucomicrobia. However, antibiotic intervention almost offset the alleviation of AS by PCA2 and prevented the biotransformation of PCA2 by gut microbiota, thus resulting in a 2327.21−6.27-fold decrease in its microbial metabolites of plasma. There was a marked correlation among the microbiota composition, the bioavailability of PCA2-derived microbial metabolites, and AS indicators. The findings indicate that the gut microbiota robustly influences the bioavailability of microbial metabolites that may partially drive the AS resilience property of PCA2.

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