4.7 Review

Urolithins: A Prospective Alternative against Brain Aging

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Ellagic acid and intestinal microflora metabolite urolithin A: A review on its sources, metabolic distribution, health benefits, and biotransformation

Mengwei Zhang et al.

Summary: Foods rich in ellagic tannins are converted into urolithin A in the stomach and small intestine, which has various beneficial biological effects. Differences in urolithin production capacity among individuals highlight the significance of exploring its biological functions, responsible strains, and corresponding functional genes.

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Urolithin A exhibits a neuroprotective effect against Alzheimer's disease by inhibiting DYRK1A activity

Huang-Ju Tu et al.

Summary: Alzheimer's disease (AD) affects more than 50 million people worldwide, but current drugs are not effective in improving cognitive impairment in AD patients. Urolithin A (UA), obtained from ellagic acid and ellagitannin, has been found to have neuroprotective effects in AD animal models. This study reveals that UA inhibits the activity of DYRK1A, a protein associated with AD, and improves memory impairment in an AD-like mouse model. These findings suggest that UA could be a potential therapeutic option for AD patients.

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Article Food Science & Technology

The profile of buckwheat tannins based on widely targeted metabolome analysis and pharmacokinetic study of ellagitannin metabolite urolithin A

Yao Xiao et al.

Summary: Buckwheat seeds are rich in flavonoids and phenolic acids. This study analyzed the tannins profile in buckwheat seeds and investigated the permeability mechanism of ellagitannin metabolite urolithin A (UA) through the blood brain barrier. The study also provided insights into the potential applications of buckwheat and UA.

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Review Food Science & Technology

Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota

Rocio Garcia-Villalba et al.

Summary: Urolithins, metabolites produced by the gut microbiota from polyphenols, have been extensively studied for their potential health benefits. Recent research has identified 13 urolithins and their corresponding conjugated metabolites in various human fluids and tissues. The study highlights the importance of understanding the microorganisms involved in urolithin production and the composition of gut microbiota associated with urolithin metabolism. However, further in vitro studies are needed to confirm the reported activities of urolithins.

MOLECULAR NUTRITION & FOOD RESEARCH (2022)

Article Food Science & Technology

Urolithin A Attenuates Diabetes-Associated Cognitive Impairment by Ameliorating Intestinal Barrier Dysfunction via N-glycan Biosynthesis Pathway

Yao Xiao et al.

Summary: This study investigates the effect of Urolithin A (UA) on diabetes-associated cognitive impairment in a mouse model of type 2 diabetes mellitus (T2DM) induced by a high-fat diet (HFD) and streptozotocin (STZ). The results show that UA treatment can attenuate cognitive impairment and reduce levels of metabolic endotoxemia and proinflammatory cytokines in serum. UA also suppresses gut/brain inflammation, improves gut barrier function, and restores the dysregulation of genes involved in N-glycan biosynthesis. Unlike metformin, the beneficial effects of UA are independent of the gut microbiome and short-chain fatty acids. These findings suggest that UA has the potential to be a novel pharmacological target for diabetes therapy by manipulating the gut-brain axis and N-glycan metabolism.

MOLECULAR NUTRITION & FOOD RESEARCH (2022)

Article Cell Biology

Urolithin A alleviates blood-brain barrier disruption and attenuates neuronal apoptosis following traumatic brain injury in mice

Qiu-Yuan Gong et al.

Summary: Urolithin A (UA), a natural metabolite, has neuroprotective effects. This study showed that UA decreased brain edema, increased tight junction protein expression, and promoted neuronal autophagy. In addition, UA reduced neuroinflammation by inhibiting two signaling pathways and improved neurological function in mice.

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Urolithin A protects dopaminergic neurons in experimental models of Parkinson's disease by promoting mitochondrial biogenesis through the SIRT1/PGC-1α signaling pathway

Jia Liu et al.

Summary: UA, a gut metabolite produced from ellagic acid-containing foods, shows potential protective effects against PD by promoting mitochondrial biogenesis and preventing neurotoxicity induced by 6-OHDA. This study provides new insights into the role of UA in regulating mitochondrial dysfunction in PD and suggests potential therapeutic applications.

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A Synergistic Combination of DHA, Luteolin, and Urolithin A Against Alzheimer's Disease

Dona P. W. Jayatunga et al.

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Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults A Randomized Clinical Trial

Sophia Liu et al.

Summary: This randomized clinical trial investigated the effects of urolithin A supplementation on aging-related decline in muscle function. The results showed that urolithin A was safe and well-tolerated, and it improved muscle endurance and plasma biomarkers associated with cellular health. However, it did not significantly improve the 6-minute walk distance and maximal ATP production in hand muscles compared to the placebo. Further research is needed to confirm these findings.

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Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population

Anurag Singh et al.

Summary: This study investigates the prevalence of UA producers in a healthy population and the effectiveness of direct UA supplementation in overcoming microbiome variability. Results show that 40% of subjects converted precursor compounds into UA after consuming pomegranate juice. UA producers were characterized by higher gut microbiome diversity and a specific bacteria ratio. Direct supplementation significantly increased plasma UA levels, providing a >6-fold exposure compared to PJ.

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Summary: Urolithins, gut metabolites produced from ellagitannin-rich foods, have various biological activities and potential therapeutic benefits in treating diseases, with antiaging activity being of particular interest.

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Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model

Jingru Qiu et al.

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

Sudhir Kshirsagar et al.

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Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

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Urolithins: potential biomarkers of gut dysbiosis and disease stage in Parkinson's patients

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Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis

Hyun Jik Lee et al.

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Andreia Barroso et al.

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Differential Effects of Whole Red Raspberry Polyphenols and Their Gut Metabolite Urolithin A on Neuroinflammation in BV-2 Microglia

Ashley Mulcahy Toney et al.

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Design, synthesis, and biological evaluation of new urolithin amides as multitarget agents against Alzheimer's disease

Karar T. Shukur et al.

Summary: A series of urolithin amide derivatives were synthesized and evaluated for their inhibitory potential on cholinesterases and MAO-B. The most potent inhibitors were identified, and docking studies revealed their binding modes with the targets. These compounds showed potential for multitarget ligand design in Alzheimer's disease drug development.

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The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice

Peng Chen et al.

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Carsten Esselun et al.

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