Research
Urolithin A
45 peer-reviewed studies curated from PubMed and Semantic Scholar.
Studies
Sorted by quality and recency
Targeting aging with urolithin A in humans: A systematic review.
Systematic review of urolithin A (UA) in humans, assessing its geroprotective effects. In five studies with 250 healthy individuals, UA showed a dose-dependent anti-inflammatory effect, upregulated mitochondrial genes, and increased muscle strength and endurance. It did not affect mitochondrial ATP production, biogenesis, dynamics, or gut microbiota composition. No significant effects on anthropometrics, cardiovascular outcomes, or physical function were observed.
The Therapeutic Relevance of Urolithins, Intestinal Metabolites of Ellagitannin-Rich Food: A Systematic Review of In Vivo Studies.
Systematic review of 41 animal studies on urolithins, metabolites of ellagitannin-rich foods, highlighting their neuroprotective, anti-metabolic disorder, nephroprotective, myocardial protective, anti-inflammatory, and musculoskeletal protective effects. Urolithin A is noted for its potential as a natural mitophagy inducer for anti-ageing.
Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial.
This randomized, double-blind, placebo-controlled trial studied the effects of urolithin A (UA) supplementation on age-related immune decline in 50 healthy middle-aged adults. UA expanded peripheral naive-like CD8 cells, increased CD8 fatty acid oxidation capacity, and augmented mitochondrial biogenesis, among other immune benefits, suggesting its potential to counteract age-related immune decline.
Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.
This randomized clinical trial investigated the effects of urolithin A supplementation on muscle endurance and mitochondrial health in older adults. Urolithin A significantly improved muscle endurance in hand and leg muscles and decreased plasma levels of certain biomarkers, but did not significantly improve the 6-minute walk distance or maximal ATP production compared to placebo. The study suggests potential benefits of urolithin A for counteracting age-associated muscle decline.
Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.
Randomized, placebo-controlled trial in middle-aged adults administering Urolithin A (Mitopure) for 4 months. Significant improvements in muscle strength, aerobic endurance, and physical performance were observed, along with reduced plasma acylcarnitines and C-reactive proteins, indicating higher mitochondrial efficiency and reduced inflammation.
Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population.
RCT investigating the prevalence of Urolithin A (UA) producers in a healthy population and the effect of direct UA supplementation. Only 12% of subjects had detectable UA levels at baseline, but direct supplementation significantly increased plasma levels, providing a >6-fold exposure compared to pomegranate juice.
Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners.
This double-blind, placebo-controlled clinical trial evaluated the effects of Urolithin A supplementation on running performance, recovery, and mitochondrial biomarkers in 42 highly trained male distance runners. While Urolithin A did not significantly improve running performance, it lowered perceived exertion and reduced markers of muscle damage, suggesting enhanced recovery.
Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study.
An 8-week randomized, double-blind, placebo-controlled study on 20 resistance-trained male athletes assessed the effects of Urolithin A supplementation. The UA group showed significant improvements in muscle endurance and strength, as well as a decrease in oxidative stress and inflammation markers compared to the placebo group.
Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial.
A randomized, double-blind, placebo-controlled crossover trial on 10 patients with heart failure with reduced ejection fraction evaluated the effects of Urolithin A (500 mg BID) over two 4-week intervention periods. The study found no significant effect on echocardiographic measures or most biochemical indices, except for an increase in serum HDL-C levels with Urolithin A compared to placebo.
The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.
First-in-human clinical trial of urolithin A (UA) in healthy, sedentary elderly individuals. UA was administered as a single dose or multiple doses over 4 weeks, showing a favorable safety profile and bioavailability. UA modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression, indicating improved mitochondrial and cellular health.
ORALLY ADMINISTERED UROLITHIN A IS SAFE AND MODULATES MUSCLE AND MITOCHONDRIAL BIOMARKERS IN ELDERLY
Phase I RCT in 60 elderly subjects assessing the safety and effects of orally administered Urolithin A (UA) on muscle and mitochondrial biomarkers. UA was well tolerated with no serious adverse effects and modulated biomarkers linked to mitochondrial and muscle function, suggesting potential benefits for muscle and mitochondrial health during aging.
Microbiota-derived urolithin A in monoclonal gammopathies and multiple myeloma therapy
Retrospective cohort study of 45 patients with multiple myeloma or premalignant disease analyzing urolithins and microbiota. Urolithin A (UroA) was found to be cytotoxic against MM cell lines, modulate cell cycle and mitochondrial activity, and inhibit proliferation of primary MM cells in vitro and in a xenograft mouse model, improving survival. Combination therapy with UroA and bortezomib showed synergistic effects even in bortezomib-resistant cases.
Diet-derived urolithin A is produced by a dehydroxylase encoded by human gut Enterocloster species
The study identifies Enterocloster species and the ucd operon as key contributors to the production of Urolithin A, a compound derived from dietary ellagitannins by the gut microbiota. It uses a multi-omics approach to uncover the mechanisms of urolithin metabolism, highlighting the role of a specific dehydroxylase enzyme complex in this process.
Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers.
The study investigates the effects of urolithin A (UA) on cardiovascular health. Preclinically, UA reduced cardiac dysfunction and improved mitochondrial quality in aging and heart failure models. In humans, UA supplementation for 4 months reduced plasma ceramides linked to CVD risks, suggesting UA's potential to support cardiovascular function.
Urolithin A increases the natural killer activity of PBMCs in patients with prostate cancer
The study investigates the potential of urolithin A to enhance the natural cytotoxicity of PBMCs in prostate cancer patients and healthy subjects. Urolithin A increased the NK activity of PBMCs by an average of 23% and modulated cytokine production, suggesting a role for the AhR in this enhancement.
Urolithin Α modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing
The study investigates the effects of Urolithin A (UA), a gut-derived metabolite, on inter-organellar communication and mitophagy. UA was found to restore inter-organellar communication via calcium signaling, promoting mitophagy, healthspan, and longevity in Caenorhabditis elegans and mammalian cells. The study highlights UA's role in enhancing mitochondrial biogenesis and mitigating stress-induced senescence.
Urolithin A ameliorates schizophrenia-like behaviors and cognitive impairments in female rats by modulating NLRP3 signaling.
The study investigates the effects of Urolithin A (UA) on schizophrenia-like behaviors and cognitive impairments in female rats. UA treatment reversed the expression of inflammatory proteins and microglial activation induced by MK801, suggesting its potential as a dietary supplement to prevent cognitive deficits in schizophrenia.
Urolithin A suppressed osteosarcoma cell migration and invasion via targeting MMPs and AKT1
The study explores the anti-metastatic potential of urolithin A (UA) against osteosarcoma cells. UA was shown to significantly inhibit migration and invasion of osteosarcoma cells, enhance cell adhesion, and reduce enzymatic activity of MMP2 and MMP9. These effects suggest UA as a promising therapeutic candidate for targeting osteosarcoma metastasis.
Urolithin-A supplementation alleviates sepsis-induced acute lung injury by reducing mitochondrial dysfunction and modulating macrophage polarization.
The study investigated the protective effects of Urolithin-A against sepsis-induced acute lung injury (ALI) in LPS-stimulated RAW264.7 macrophages and mouse models. Urolithin-A reduced mitochondrial dysfunction, ROS, NO production, and apoptosis, while enhancing mitophagy and preserving mitochondrial function. In vivo, it reduced lung injury and inflammation, improved epithelial barrier integrity, and upregulated anti-apoptotic markers.
Urolithin A alleviates NLRP3 inflammasome activation and pyroptosis by promoting microglial mitophagy following spinal cord injury.
The study investigated the effects of Urolithin A (UA) on spinal cord injury (SCI) in a mouse model. UA treatment inhibited NLRP3 inflammasome activation and pyroptosis, restored mitochondrial activity, and promoted mitophagy, highlighting its protective role against SCI-induced inflammation.
Urolithin A alleviates radiation pneumonitis by activating PINK1/PRKN-mediated Mitophagy.
The study investigates the role of PINK1/PRKN-mediated mitophagy in radiation pneumonitis (RP) and evaluates the therapeutic potential of Urolithin A (UA) in regulating inflammation. In RP mouse models and radiation-induced cell models, UA improved lung pathology, reduced inflammatory cytokine levels, and inhibited excessive activation of the RIG-I/MDA5-MAVS pathway through mitophagy activation.
Urolithin A enhances diabetic wound healing: Insights from parkin-mediated mitophagy in endothelial progenitor cells.
The study investigates the effects of Urolithin A on diabetic wound healing, focusing on mitochondrial dysfunction and endothelial progenitor cell function in high glucose conditions. Urolithin A was found to upregulate Parkin, activate mitophagy, and improve delayed wound healing in diabetic rat models.
Urolithin a attenuates rheumatoid arthritis by inhibiting inflammation and pyroptosis in fibroblasts via the AMPK/ NF-κB signaling pathway.
The study investigates the effects of Urolithin A (UA) on rheumatoid arthritis using a CIA model in DBA mice and LPS-stimulated NIH/3T3 cells. UA significantly reduced arthritis scores, inhibited inflammation, pannus formation, and cartilage and bone destruction in mice, and counteracted LPS-induced effects in vitro, suggesting UA as a promising treatment for RA.
Urolithin-A Derivative UAS03 Improves Cognitive Deficits and Memory by Activating Nrf2 Pathways to Alleviate Oxidative Stress and Neuroinflammation.
Animal study investigating the neuroprotective effects of UAS03, a synthetic analogue of Urolithin-A, on LPS-induced neuroinflammation in mice. UAS03 improved cognitive and memory functions, reduced depressive symptoms, and mitigated oxidative stress and neuroinflammation through activation of the Nrf2 signaling pathway.
The polyphenol metabolite urolithin A suppresses myostatin expression and augments glucose uptake in human skeletal muscle cells
In vitro study on the effects of urolithin A (UA) on human skeletal muscle cells. UA treatment enhanced both basal- and insulin-stimulated glucose uptake and reduced myostatin expression, suggesting potential metabolic benefits.
Urolithin a improves Parkinson's disease-associated cognitive impairment through modulation of neuroinflammation and neuroplasticity.
The study investigates the effect of Urolithin A (UA) on cognitive impairment in Parkinson's disease (PD) using MPTP-induced PD mouse model and transgenic mice overexpressing human A53T mutant α-synuclein. UA treatment reversed cognitive dysfunction and was associated with decreased neuroinflammation and reduced synaptic damage. The beneficial effects involve activation of the AKT/CREB/BDNF signaling pathway, suggesting UA's potential as a dietary supplement for cognitive deficits in PD.
Urolithin A and nicotinamide riboside differentially regulate innate immune defenses and metabolism in human microglial cells
The study investigates the effects of Urolithin A and Nicotinamide Riboside on immune signaling, mitochondrial function, and microglial activity in a human microglial cell line. Both compounds reduced DNA damage-induced cellular senescence and improved mitochondrial respiration, with distinct effects on neuroinflammation and mitochondrial dynamics.
Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions
The study investigated the effects of Urolithin A (UA) on Alzheimer's disease in three mouse models. Long-term UA treatment improved learning, memory, and olfactory function, reduced Aβ and Tau pathologies, and enhanced long-term potentiation. UA activated autophagy/mitophagy by improving lysosomal functions, highlighting its potential therapeutic effects in AD.
Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model.
The study investigates the effects of Urolithin A (UA) on Parkinson's disease models. UA treatment reduced dopaminergic neuron loss, ameliorated behavioral deficits, and decreased neuroinflammation in an MPTP mouse model of PD. UA also promoted mitophagy, restored mitochondrial function, and reduced NLRP3 inflammasome activation in BV2 microglial cells exposed to LPS.
Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis
The study investigates the effects of Urolithin A on osteoarthritis (OA), showing that it improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in a mouse model of OA. Urolithin A enhanced mitophagy and mitochondrial respiration in primary chondrocytes and decreased disease progression, synovial inflammation, and pain in OA mice.
Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy.
The study investigates the effect of Urolithin A (UA) on T memory stem cells (TSCM) and its role in enhancing anti-tumor immunity. Oral administration of UA to tumor-bearing mice improved CD8+ T cell immunity, and ex vivo UA pre-treated T cells showed enhanced anti-tumor function upon adoptive transfer. UA-induced TSCM formation involved Pink1-mediated mitophagy and Wnt signaling.
Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy
The study investigates the effects of urolithin A, a mitophagy activator, on muscle function in models of Duchenne muscular dystrophy (DMD). Urolithin A improved mitochondrial respiration, muscle stem cell regeneration, and muscle function in DMD models, suggesting potential therapeutic applications for muscular dystrophies.
Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor
The study demonstrates the therapeutic effect of Urolithin A (URA) in an experimental autoimmune encephalomyelitis (EAE) animal model. Oral URA suppressed disease progression and reduced inflammation in the central nervous system by targeting the Aryl Hydrocarbon Receptor (AhR) and modulating signaling pathways.
Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functions.
In vitro study comparing urolithin A, iso-urolithin A, and urolithin B with their glucuronides on inflammatory response in macrophages and neutrophils. Urolithin A was the most active in inhibiting LPS-induced inflammatory response, while glucuronides showed no activity.
Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice
The study investigates the effects of urolithin A (UA) on diet-induced obesity and metabolic dysfunctions in mice. UA treatment enhances thermogenesis in brown adipose tissue and induces browning of white adipose tissue, leading to increased energy expenditure and prevention of weight gain. The effects are linked to elevated triiodothyronine levels, and are reversible with thyroid hormone inhibition.
Unveiling the potential of Urolithin A in Cancer Therapy: Mechanistic Insights to Future Perspectives of Nanomedicine
This narrative review explores the anticancer mechanisms of Urolithin A (UA), a metabolite derived from ellagic acid, and its potential as a therapeutic agent in cancer treatment. It discusses UA's regulation of autophagy, enhancement of mitochondrial function, and inhibition of tumor progression, as well as advances in nanoformulation strategies to improve its therapeutic benefits.
Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges
This review summarizes the biosynthesis, pharmacokinetic profile, and biological effects of Urolithin A (UA), highlighting its potential therapeutic applications in CNS disorders like Alzheimer's, Parkinson's, and stroke. It discusses UA's promotion of mitophagy, mitochondrial homeostasis, and its anti-inflammatory, antioxidant, anti-senescence, and anti-apoptotic properties, along with challenges in clinical translation.
Bioengineering the metabolic network of CAR T cells with GLP-1 and Urolithin A increases persistence and long-term anti-tumor activity
The study investigates the metabolic reprogramming of CAR T cells using GLP-1R agonist (semaglutide) and Urolithin A to enhance autophagy and mitophagy, improving persistence and anti-tumor activity. The combination activates autophagy through mTOR inhibition and mitophagy via Atg4b activation, increasing CD8+ T memory cells and reducing cytokine release syndrome risks.
Emerging evidence of Urolithin A in sports nutrition: bridging preclinical findings to athletic applications
Narrative review discussing Urolithin A (UA) as a novel sports nutrition supplement with benefits including osteoprotective effects, reduced joint degeneration, and enhanced muscle endurance. UA enhances mitochondrial β-oxidation and AMPK signaling, suggesting ergogenic effects. Human trials are needed to validate these claims.
Impact of the Natural Compound Urolithin A on Health, Disease, and Aging.
Narrative review of Urolithin A (UA), a natural compound derived from ellagitannins and ellagic acid, exploring its impact on aging and disease. UA enhances cellular health by increasing mitophagy and mitochondrial function, reducing inflammation, and showing protective effects against age-related conditions in preclinical studies and clinical trials.
Induction of Autophagy and Activation of SIRT-1 Deacetylation Mechanisms Mediate Neuroprotection by the Pomegranate Metabolite Urolithin A in BV2 Microglia and Differentiated 3D Human Neural Progenitor Cells.
The study investigates the neuroprotective and anti-inflammatory effects of urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells. Urolithin A reduces nitrite, TNF-α, and IL-6 production, and its effects are mediated by SIRT-1 activation and autophagy induction.
Urolithin A Is a Dietary Microbiota-Derived Human Aryl Hydrocarbon Receptor Antagonist
The study investigates urolithin A (UroA), a gut microbiota-derived metabolite, as an antagonist of the aryl hydrocarbon receptor (AHR). UroA and B were shown to antagonize TCDD-induced AHR-mediated transcriptional activity and attenuate cytokine-induced expression of IL6 and PTGS2 in Caco-2 cells, suggesting anti-inflammatory effects mediated through AHR.
Urolithin A, a Novel Natural Compound to Target PI3K/AKT/mTOR Pathway in Pancreatic Cancer
The study investigates Urolithin A, a natural compound derived from pomegranates, targeting the PI3K/AKT/mTOR signaling pathways in pancreatic ductal adenocarcinoma (PDAC). Urolithin A blocked phosphorylation of AKT and p70S6K in vitro, inhibited tumor growth in xenografts, and increased survival in PKT mice compared to vehicle or gemcitabine therapy. It also reprogrammed the tumor microenvironment by reducing immunosuppressive cell populations.
Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases
The study investigates the biological activities of Urolithin A, a metabolite derived from ellagic acid by gut microbiota. Urolithin A inhibits heme peroxidases more effectively than ellagic acid, reduces PMA-induced superoxide generation in neutrophils, and decreases mouse ear edema and MPO activity, suggesting benefits in reducing tissue inflammation and supporting gut health.
Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease.
The study investigates the role of mitophagy in Alzheimer's disease models, showing that mitophagy stimulation through NAD supplementation, urolithin A, and actinonin reverses memory impairment and diminishes amyloid-β and tau pathology. The findings suggest mitophagy as a potential therapeutic intervention for Alzheimer's disease.