The Utilization of Urolithin A—A Natural Polyphenol Metabolite of Ellagitannins as a Modulator of the Gut Microbiota for Its Potential Use in Obesity Therapy

Abdulrahman, Abdulrasheed O.; Alzubaidi, Mohammed Yahya; Nadeem, Muhammad; Khan, Jalaluddin A.J.; Rather, Irfan A.; Khan, Mohammad Imran

doi:10.3390/iecbm2020-08806

Cited by 3 publications

(5 citation statements)

References 29 publications

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“…Wistar rats were divided randomly into four groups (n = 6): a control group, a DOX group, a URO A at 2.5 mgkg −1 with DOX group, and a URO A at 5 mgkg −1 with DOX group ( Figure 1 ). URO A doses were based on an earlier study [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

et al. 2023

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Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg−1) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg−1 d−1) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis.

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Section: Methodsmentioning

confidence: 99%

Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

et al. 2023

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“…Measurement of Soluble Aβ Levels. We used sandwich ELISA method to detect the soluble Aβ levels, as previously described in Manczak et al 2016 [ 25 ] and Manczak et al 2018 [ 48 , 49 , 50 ]. For this method, 96-well plate was used, and the procedure was performed by following the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease

Kshirsagar

Alvir

Pradeepkiran

et al. 2022

Cells

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In the current study, for the first time, we study mitophagy enhancer urolithin A and a combination of urolithin A+green tea extract EGCG against human Aβ peptide-induced mitochondrial and synaptic, dendritic, inflammatory toxicities and behavioral changes in humanized homozygous amyloid beta knockin (hAbKI) mice of late-onset Alzheimer’s disease (AD). Our findings reveal significantly increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory. mRNA and protein levels of mitochondrial fusion, synaptic, mitophagy and autophagy genes were upregulated, and mitochondrial fission genes are downregulated in urolithin A and combine treatment in hAbKI mice; however, the effect is stronger in combined treatment. Immunofluorescence analysis of hippocampal brain sections shows similar findings of mRNA and protein levels. Mitochondrial dysfunction is significantly reduced in both treatment groups, but a stronger reduction is observed in combined treatment. Dendritic spines and lengths are significantly increased in both treatment groups, but the effect is stronger in combined treatment. The fragmented number of mitochondria is reduced, and mitochondrial length is increased, and mitophagosomal formations are increased in both the groups, but the effect is stronger in the combined treatment. The levels of amyloid beta (Aβ) 40 and Aβ42 are reduced in both treatments, however, the reduction is higher for combined treatment. These observations suggest that urolithin A is protective against human Aβ peptide-induced toxicities; however, combined treatment of urolithin A+EGCG is effective and stronger, indicating that combined therapy is promising to treat late-onset AD patients.

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“…EA metabolism and urolithin production vary according to host health, age, gut microbial composition, environmental conditions, and metabotypes [14,119,131,132]. The presence of specific bacterial genera such as Gordonibacter and Ellagibacter has been shown to be necessary for the conversion of EA into urolithins [118,119,133,134]. Two gut microbial species, Gordonibacte urolithinfaciens and Gordonibacte pamelaeae, can produce urolithin C, whereas Ellagibacter isourolithinfaciens produces isourolithin A [132,135,136].…”

Section: Ellagic Acid Metabolitesmentioning

confidence: 99%

“…New insights into research on EAs have focused on its microbial metabolites, the urolithins. According to Abdulrahman and colleagues [133], supplementation of urolithin A to HFD-fed Wistar rats, reduced bodyweight, serum levels of cholesterol and low-density lipoprotein (LDL), and increased levels of high-density lipoprotein (HDL). Moreover, this study demonstrated that urolithin A administration reduced the abundance of the specific microbiome related to weight gain, dysfunction of lipid metabolism, and impaired glucose metabolism, suggesting urolithin A has the potential to act as a therapeutic agent in obesity [133].…”

Section: Therapeutic Efficacymentioning

confidence: 99%

“…According to Abdulrahman and colleagues [133], supplementation of urolithin A to HFD-fed Wistar rats, reduced bodyweight, serum levels of cholesterol and low-density lipoprotein (LDL), and increased levels of high-density lipoprotein (HDL). Moreover, this study demonstrated that urolithin A administration reduced the abundance of the specific microbiome related to weight gain, dysfunction of lipid metabolism, and impaired glucose metabolism, suggesting urolithin A has the potential to act as a therapeutic agent in obesity [133]. A study on both EA and urolithin A has revealed that in a high-fat/highsucrose-fed mouse model, only EA demonstrated the capability to reduce proton leakage in primary hepatocytes, as opposed to urolithin A; thus, reporting its involvement in mitochondrial respiratory capacity during insulin resistance [201].…”

Section: Therapeutic Efficacymentioning

confidence: 99%

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Unlocking the Therapeutic Potential of Ellagic Acid for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

Senavirathna,

Shafaei,

Lareu

et al. 2024

Antioxidants

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Obesity is in epidemic proportions in many parts of the world, contributing to increasing rates of non-alcoholic fatty liver disease (NAFLD). NAFLD represents a range of conditions from the initial stage of fatty liver to non-alcoholic steatohepatitis (NASH), which can progress to severe fibrosis, through to hepatocellular carcinoma. There currently exists no treatment for the long-term management of NAFLD/NASH, however, dietary interventions have been investigated for the treatment of NASH, including several polyphenolic compounds. Ellagic acid is one such polyphenolic compound. Nutraceutical food abundant in ellagic acid undergoes initial hydrolysis to free ellagic acid within the stomach and small intestine. The proposed mechanism of action of ellagic acid extends beyond its initial therapeutic potential, as it is further broken down by the gut microbiome into urolithin. Both ellagic acid and urolithin have been found to alleviate oxidative stress, inflammation, and fibrosis, which are associated with NAFLD/NASH. While progress has been made in understanding the pharmacological and biological activity of ellagic acid and its involvement in NAFLD/NASH, it has yet to be fully elucidated. Thus, the aim of this review is to summarise the currently available literature elucidating the therapeutic potential of ellagic acid and its microbial-derived metabolite urolithin in NAFLD/NASH.

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The Utilization of Urolithin A—A Natural Polyphenol Metabolite of Ellagitannins as a Modulator of the Gut Microbiota for Its Potential Use in Obesity Therapy

Cited by 3 publications

References 29 publications

Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease

Unlocking the Therapeutic Potential of Ellagic Acid for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

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