Effects of Ellagic Acid Supplementation on Jejunal Morphology, Digestive Enzyme Activities, Antioxidant Capacity, and Microbiota in Mice

Abstract

Ellagic acid (EA), a plant polyphenol mainly found in nuts and fruits, exhibits various biological effects. However, the effects of EA on intestinal health remain poorly understood. Hence, the present study aimed to assess the effects of EA supplementation on jejunal morphology, digestive enzyme activities, antioxidant capacity, and microbiota in C57BL/6J mice. A total of 144 mice were randomly assigned to three treatments groups: the control (CON) group received a standard pellet diet, the 0.1% EA group received a standard pellet diet plus 0.1% EA, and the 0.3% EA group received a standard pellet diet plus 0.3% EA. The mice were killed at the end of the experimental period, and jejunal samples were collected. The results revealed that the mice in the 0.3% EA group had higher (P < 0.05) average daily gain and greater (P < 0.05) jejunal villus height than those in the CON group. In addition, the jejunal lactase and sucrase activities were higher (P < 0.05) in the 0.1% EA and 0.3% EA groups, and the alkaline phosphatase activity was higher (P < 0.05) in the 0.3% EA group than in the CON group. Compared with the CON group, the administration of EA increased (P < 0.05) the superoxide dismutase and catalase activities but decreased (P < 0.05) the malonaldehyde content in the jejunum. Moreover, the jejunal messenger RNA expression levels of nuclear factor-E2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) were higher (P < 0.05) in the 0.3% EA group than in the CON group. Furthermore, compared with the CON group, the count of Escherichia coli decreased (P < 0.05), and that of Lactobacillus species increased (P < 0.05) in the 0.3% EA group. In general, our findings indicate that the administration of EA can enhance the growth of mice, promote intestinal development, increase the antioxidant capacity, and regulate the intestinal microbiota.

Ellagic Acid Alleviates Oxidative Stress by Mediating Nrf2 Signaling Pathways and Protects against Paraquat-Induced Intestinal Injury in Piglets

“…Since EA could either prevent oxidation by acting as free-radical scavengers or retard the oxidation process by acting through indirect pathway, it has been classified as the multi-function antioxidant. In several well-designed chronic and degenerative disease models, EA displays the capability to lower the oxidative stress markers, such as malondialdehyde (MDA) and nitric oxide, and to increase the antioxidant enzyme (e.g., catalase (CAT), superoxide dismutase (SOD)) activities [ 4 , 5 , 6 , 7 , 8 ]. Meanwhile, there is a widespread tendency to suggest that the antioxidative benefit rendered by EA in vivo is due to its gut microbial metabolites, urolithins [ 9 , 10 ].…”

“…However, in vivo, the beneficial effects of EA supplementation on the damaged intestinal barrier induced by oxidative stress are not clear, and its acting target still needs to be further demonstrated. Meanwhile, previous study have shown that EA can protect against oxidative stress in mice through the Nrf2/HO-1 pathway [ 8 ], but it is not common to use pigs as research subjects.…”

Dietary supplementation ellagic acid on the growth, intestinal immune response, microbiota, and inflammation in weaned piglets

“…Specific doses of EA have been shown to increase the weight of normal mice. Moreover, EA alleviates the symptoms of colitis and even has a therapeutic effect in a mouse model of colitis (9). These findings indicate that EA has anti-inflammatory effects and positively influences animal growth.…”

Relationship between Dietary Polyphenols and Gut Microbiota: New Clues to Improve Cognitive Disorders, Mood Disorders and Circadian Rhythms

“…In addition, urolithins suppressed NF-κB activity and the phosphorylation of JNK, ERK and Akt and mRNA levels of proinflammatory TNF-α, IL-6, IL-1β, iNOS and COX-2 genes [ 101 ] and increased the production of the anti-inflammatory cytokine IL-10 and the phosphorylation of AMP-activated protein kinase (AMPK), which is associated with anti-inflammatory and antioxidant activities [ 102 ]. Ellagic acid regulated intestinal microbiota through increasing Lactobacillus species and decreasing Escherichia coli levels [ 103 ], enhanced the immune response by modulating different signalling pathways and increasing the intestinal mucosal barrier function via activating Zonula occludens-1 and Occludin proteins, which are implicated in the tight junction structure of enterocytes and intestinal permeability [ 104 ]. Following polyphenol treatment, mitochondrial dysfunction and the levels of some neuroinflammatory biomarkers were reduced in mouse brains, and dendritic spines and lengths were significantly increased [ 105 ].…”