Ameliorative Effect of Ellagic Acid on Aging in Rats with the Potential Mechanism Relying on the Gut Microbiota and Urolithin A-Producing Ability

Abstract

Ellagic acid (EA) exhibits potential antiaging activity. Differences in individual ability to produce urolithins may result in large interindividual variability in the health effects of EA. Therefore, the effects and mechanism of EA on d-galactose-induced aging, considering urolithin A-producing ability, were investigated. Our results showed that EA improved cognitive impairment and hippocampal damage, increased the GABA (by 107.84–117.86%) and 5-HT (by 72.56–100.85%) levels, and suppressed the inflammatory and oxidative stress in aging rats. Thirteen plasma metabolites and 12 brain metabolites were improved by EA administration in aging rats. In particular, EA showed a better anti-aging effect in high-UroA-producing rats than in the low counterparts, while antibiotic intervention almost offset EA-alleviated aging induced by d-gal. Furthermore, the lower ratio of Firmicutes and Bacteroidota as well as the greater abundances of Akkermansia (by 139.21%), Bifidobacterium (by 88.04%), Clostridium_sensu_stricto_1 (by 183.47%), Lactobacillus (by 97.23%), and Turicibacter (by 83.06%) were observed in the high-UroA-producing group compared with the model group (p < 0.05). These findings provide novel insights into the anti-aging effects of EA and suggest that the ability of the gut microbiota responding to EA largely determines EA’s anti-aging performance.

Inhibition of the NF-κB and mTOR targets by urolithin A attenuates d-galactose-induced aging in mice

“…2E). 2 Compared with the model group, the M-Uro-A group and H-Uro-A group showed significant increases of 92.14% and 238.11% in their DI towards the novel object, respectively ( p < 0.05).…”

“…The discrimination index (DI) = ( N − F )/( N + F ) × 100% of object 3 was calculated, and their cognitive capacity was evaluated by DI. 2 The experimental design diagram of the new object recognition system is shown in Fig. 2D.…”

“…This natural process is referred to as aging. 2 Oxidative stress and inflammatory reactions are important factors in aging. 3 In the process of aging, these reactions may induce age-related functional decline in areas such as motor function and cognition, ultimately leading to degenerative diseases such as sarcopenia and Alzheimer's disease.…”

Plant miRNA bol-miR159 Regulates Gut Microbiota Composition in Mice: In Vivo Evidence of the Crosstalk between Plant miRNAs and Intestinal Microbes

“…In mice supplemented with miR159, although the decrease in Firmicutes and the increase in Bacteroidetes were not significant, Firmicutes-to-Bacteroidetes ratio (F/B ratio) was significantly lowered comparing to that in the CD group (Figure I, p < 0.01). This suggested that miR159 supplementation might have potential in maintaining normal intestinal homeostasis …”

Anti-Aging Potential of Bioactive Phytoconstituents Found in Edible Medicinal Plants: A Review

“…The study also emphasized the significant protection provided by ellagic acid at a concentration of 10 µM in terms of cell proliferation and TNF-α levels. Xian et al [206] reported that ellagic acid ameliorated cognitive impairment and hippocampal damage, elevated GABA and 5-HT levels, and suppressed inflammation and oxidative stress in a D-galactose-induced aging rat model. Furthermore, Naghibi et al [207] discovered that ellagic acid treatment increased the levels of antioxidant enzymes and reduced malondialdehyde concentration.…”