Health functions and related molecular mechanisms of ellagitannin-derived urolithins

References

• Abdelazeem, K. M., M. Z. Kalo, S. Beer-Hammer, and F. Lang. 2021. The gut microbiota metabolite urolithin A inhibits NF-kB activation in LPS stimulated BMDMs. Scientific Reports 11 (1): 1–16. doi: 10.1038/s41598-021-86514-6.
   PubMed Web of Science ®Google Scholar
• Adachi, S.-I., K. Sasaki, S. Kondo, W. Komatsu, F. Yoshizawa, H. Isoda, and K. Yagasaki. 2020. Antihyperuricemic effect of urolithin A in cultured hepatocytes and model mice. Molecules 25 (21):5136–51. doi: 10.3390/molecules25215136.
   PubMed Web of Science ®Google Scholar
• Ahsan, A., Y.-R. Zheng, X. L. Wu, W. D. Tang, M. R. Liu, S. J. Ma, L. Jiang, W. W. Hu, X. N. Zhang, and Z. Chen. 2019. Urolithin A-activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo. CNS Neuroscience & Therapeutics 25 (9):976–86. doi: 10.1111/cns.13136.
   PubMed Web of Science ®Google Scholar
• Alauddin, M., T. Okumura, J. Rajaxavier, S. Khozooei, S. Pöschel, S. Takeda, Y. Singh, S. Y. Brucker, D. Wallwiener, A. Koch, et al. 2020. Gut bacterial metabolite urolithin A decreases actin polymerization and migration in cancer cells. Molecular Nutrition & Food Research 64 (7):1900390. doi: 10.1002/mnfr.201900390.
   Web of Science ®Google Scholar
• Andreux, P. A., W. Blanco-Bose, D. Ryu, F. Burdet, M. Ibberson, P. Aebischer, J. Auwerx, A. Singh, and C. Rinsch. 2019. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism 1 (6):595–603. doi: 10.1038/s42255-019-0073-4.
   PubMedGoogle Scholar
• Bakkalbaşi, E., O. Menteş, and N. Artik. 2009. Food ellagitannins-occurrence, effects of processing and storage. Critical Reviews in Food Science and Nutrition 49 (3):283–98. doi: 10.1080/10408390802064404.
   PubMed Web of Science ®Google Scholar
• Bayle, M., C. Roques, B. Marion, M. Audran, C. Oiry, F. M. M. Bressolle-Gomeni, and G. Cros. 2016. Development and validation of a liquid chromatography-electrospray ionization-tandem mass spectrometry method for the determination of urolithin C in rat plasma and its application to a pharmacokinetic study. Journal of Pharmaceutical and Biomedical Analysis 131 (30):33–9. doi: 10.1016/j.jpba.2016.07.046.
   PubMedGoogle Scholar
• Bayle, M., J. Neasta, M. Dall'Asta, G. Gautheron, A. Virsolvy, J.-F. Quignard, E. Youl, R. Magous, J.-F. Guichou, A. Crozier, et al. 2019. The ellagitannin metabolite urolithin C is a glucose-dependent regulator of insulin secretion through activation of L-type calcium channels. British Journal of Pharmacology 176 (20):4065–78. doi: 10.1111/bph.14821.
   PubMed Web of Science ®Google Scholar
• Beltran, D., M. Romo-Vaquero, J. C. Espin, F. A. Tomas-Barberan, and M. V. Selma. 2018. Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family eggerthellaceae, isolated from human gut. International Journal of Systematic and Evolutionary Microbiology 68 (5):1707–12. doi: 10.1099/ijsem.0.002735.
   PubMed Web of Science ®Google Scholar
• Bhat, Z. Y., P. Cadnapaphornchai, K. Ginsburg, M. Sivagnanam, S. Chopra, C. K. Treadway, H. S. Lin, G. Yoo, A. Sukari, and M. D. Doshi. 2015. Understanding the risk factors and long-term consequences of cisplatin-associated acute kidney injury: an observational cohort study. PLoS One 10 (11):e0142225–9. doi: 10.1371/journal.pone.0142225.
   PubMed Web of Science ®Google Scholar
• Boakye, Y. D., L. Groyer, and E. H. Heiss. 2018. An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages. Biochimica et Biophysica Acta. General Subjects 1862 (1):61–70. doi: 10.1016/j.bbagen.2017.10.006.
   PubMed Web of Science ®Google Scholar
• Boyd, A. W., P. F. Bartlett, and M. Lackmann. 2014. Therapeutic targeting of EPH receptors and their ligands. Nature Reviews. Drug Discovery 13 (1):39–62. doi: 10.1038/nrd4175.
   PubMed Web of Science ®Google Scholar
• Bratic, A, and N. G. Larsson. 2013. The role of mitochondria in aging. The Journal of Clinical Investigation 123 (3):951–7. doi: 10.1172/JCI64125.
   PubMed Web of Science ®Google Scholar
• Cai, Y. Z., S. Mei, X. Jie, Q. Luo, and H. Corke. 2006. Structure-radical scavenging activity relationships of phenolic compounds from traditional chinese medicinal plants. Life Sciences 78 (25):2872–88. doi: 10.1016/j.lfs.2005.11.004.
   PubMed Web of Science ®Google Scholar
• Cao, S.-Y., C.-N. Zhao, X.-Y. Xu, G.-Y. Tang, H. Corke, R.-Y. Gan, and H.-B. Li. 2019. Dietary plants, gut microbiota, and obesity: effects and mechanisms. Trends in Food Science & Technology 92 (2019):194–204. doi: 10.1016/j.tifs.2019.08.004.
   Google Scholar
• Cao, S. Y., B. Y. Li, R. Y. Gan, Q. Q. Mao, Y. F. Wang, A. Shang, J. M. Meng, X. Y. Xu, X. L. Wei, and H. B. Li. 2020. The in vivo antioxidant and hepatoprotective actions of selected Chinese teas. Foods 9 (3):262–23. doi: 10.3390/foods9030262.
   PubMed Web of Science ®Google Scholar
• Cásedas, G., F. Les, C. Choya-Foces, M. Hugo, and V. López. 2020. The metabolite urolithin-A ameliorates oxidative stress in neuro-2a cells, becoming a potential neuroprotective agent. Antioxidants 9 (2):177–93. doi: 10.3390/antiox9020177.
   Web of Science ®Google Scholar
• Chen, P., F. Chen, J. Lei, Q. Li, and B. Zhou. 2019. Activation of the miR-34a-mediated SIRT1/mTOR signaling pathway by urolithin A attenuates D-galactose-induced brain aging in mice. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics 16 (4):1269–82. doi: 10.1007/s13311-019-00753-0.
   PubMed Web of Science ®Google Scholar
• Chen, P., J. Lei, F. Chen, and B. Zhou. 2020. Ameliorative effect of urolithin A on D-gal-induced liver and kidney damage in aging mice via its antioxidative, anti-inflammatory and antiapoptotic properties. RSC Advances 10 (14):8027–38. doi: 10.1039/d0ra00774a.
   PubMed Web of Science ®Google Scholar
• Cheng, F., J. Dou, Y. Zhang, X. Wang, H. Wei, Z. Zhang, Y. Cao, and Z. Wu. 2021. Urolithin A inhibits epithelial–mesenchymal transition in lung cancer cells via P53-Mdm2-snail pathway. OncoTargets and Therapy 14 (14):3199–208. doi: 10.2147/OTT.S305595.
   PubMedGoogle Scholar
• Cohen, E. E. W., R. B. Bell, C. B. Bifulco, B. Burtness, M. L. Gillison, K. J. Harrington, Q. T. Le, N. Y. Lee, R. Leidner, R. L. Lewis, et al. 2019. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). Journal for Immunotherapy of Cancer 7 (1):184. doi: 10.1186/s40425-019-0662-5.
   PubMed Web of Science ®Google Scholar
• Crudo, F., A. Barilli, P. Mena, B. M. Rotoli, D. Del Rio, C. Dall'Asta, and L. Dellafiora. 2021. An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C. Toxicology Letters 340 (2021):15–22. doi: 10.1016/j.toxlet.2021.01.007.
   PubMedGoogle Scholar
• Cruz-Jentoft, A. J., G. Bahat, J. Bauer, Y. Boirie, O. Bruyère, T. Cederholm, C. Cooper, F. Landi, Y. Rolland, A. A. Sayer, Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2, et al. 2019. Sarcopenia: revised European consensus on definition and diagnosis. Age and Ageing 48 (1):16–31. doi: 10.1093/ageing/afy169.
   PubMed Web of Science ®Google Scholar
• Cui, G. H., W. Q. Chen, and Z. Y. Shen. 2018. Urolithin A shows anti-atherosclerotic activity via activation of class B scavenger receptor and activation of Nef2 signaling pathway. Pharmacological Reports 70 (3):519–24. doi: 10.1016/j.pharep.2017.04.020.
   PubMed Web of Science ®Google Scholar
• Dahiya, N. R., B. Chandrasekaran, V. Kolluru, M. Ankem, C. Damodaran, and M. V. Vadhanam. 2018. A natural molecule, urolithin A, downregulates androgen receptor activation and suppresses growth of prostate cancer. Molecular Carcinogenesis 57 (10):1332–41. doi: 10.1002/mc.22848.
   PubMed Web of Science ®Google Scholar
• Dellafiora, L., M. Milioli, A. Falco, M. Interlandi, A. Mohamed, M. Frotscher, B. Riccardi, P. Puccini, D. Del Rio, G. Galaverna, et al. 2020. A hybrid in silico/in vitro target fishing study to mine novel targets of urolithin A and B: a step towards a better comprehension of their estrogenicity. Molecular Nutrition & Food Research 64 (16):2000289–31. doi: 10.1002/mnfr.202000289.
   Web of Science ®Google Scholar
• Ding, S.-L., Z.-Y. Pang, Z.-M. Chen, Z. Li, X.-X. Liu, Q.-L. Zhai, J.-M. Huang, and Z.-Y. Ruan. 2020. Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes. Journal of Inflammation (London, England) 17(:13– doi: 10.1186/s12950-020-00242-8.
   PubMed Web of Science ®Google Scholar
• Diop, E. H. A., E. F. Queiroz, L. Marcourt, S. Kicka, S. Rudaz, T. Diop, T. Soldati, and J. L. Wolfender. 2019. Antimycobacterial activity in a single-cell infection assay of ellagitannins from Combretum aculeatum and their bioavailable metabolites. Journal of Ethnopharmacology 238 (2019):111832–1. doi: 10.1016/j.jep.2019.111832.
   PubMedGoogle Scholar
• El-Wetidy, M. S., R. Ahmad, I. Rady, H. Helal, M. I. Rady, M.-A. Vaali-Mohammed, K. Al-Khayal, T. B. Traiki, and M.-H. Abdulla. 2021. Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells. Cell Stress & Chaperones 26 (3):473–93. doi: 10.1007/s12192-020-01189-8.
   PubMed Web of Science ®Google Scholar
• Espin, J. C., M. Larrosa, M. T. Garcia-Conesa, and F. Tomas-Barberan. 2013. Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far. Evidence-Based Complementary and Alternative Medicine: eCAM 2013:270418–5. doi: 10.1155/2013/270418.
   PubMed Web of Science ®Google Scholar
• Evtyugin, D. D., S. Magina, and D. V. Evtuguin. 2020. Recent advances in the production and applications of ellagic acid and its derivatives: a review. Molecules 25 (12):2745–20. doi: 10.3390/molecules25122745.
   PubMed Web of Science ®Google Scholar
• Farha, A. K., R.-Y. Gan, H.-B. Li, D.-T. Wu, A. G. Atanasov, K. Gul, J.-R. Zhang, Q.-Q. Yang, and H. Corke. 2020a. The anticancer potential of the dietary polyphenol rutin: current status, challenges, and perspectives. Critical Reviews in Food Science and Nutrition 62 (3):832–28. doi: 10.1080/10408398.2020.1829541.
   PubMed Web of Science ®Google Scholar
• Farha, A. K., Q.-Q. Yang, G. Kim, H.-B. Li, F. Zhu, H.-Y. Liu, R.-Y. Gan, and H. Corke. 2020b. Tannins as an alternative to antibiotics. Food Bioscience 38 (2020):100751–14. doi: 10.1016/j.fbio.2020.100751.
   Google Scholar
• Ferlay, J., M. Ervik, F. Lam, M. Colombet, L. Mery, and M. Piñeros. 2020. Global cancer observatory: Cancer today. Lyon: International Agency for Research on Cancer; 2020.
   Google Scholar
• Fu, X., L.-F. Gong, Y.-F. Wu, Z. Lin, B.-J. Jiang, L. Wu, and K.-H. Yu. 2019. Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1β-induced inflammatory response in human osteoarthritis: in vitro and in vivo studies. Food & Function 10 (9):6135–46. doi: 10.1039/c9fo01332.
   PubMed Web of Science ®Google Scholar
• Gandhi, G. R., G. Jothi, T. Mohana, A. B. S. Vasconcelos, M. M. Montalvao, G. Hariharan, G. Sridharan, P. M. Kumar, R. Q. Gurgel, H. B. Li, et al. 2021. Anti-inflammatory natural products as potential therapeutic agents of rheumatoid arthritis: a systematic review. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 93 (2021):153766–12. doi: 10.1016/j.phymed.2021.153766.
   PubMedGoogle Scholar
• Gandhi, G. R., A. B. S. Vasconcelos, D. T. Wu, H. B. Li, P. J. Antony, H. Li, F. Geng, R. Q. Gurgel, N. Narain, and R. Y. Gan. 2020. Citrus flavonoids as promising phytochemicals targeting diabetes and related complications: a systematic review of in vitro and in vivo studies. Nutrients 12 (10):2907–32. doi: 10.3390/nu12102907.
   PubMed Web of Science ®Google Scholar
• Gao, H., X. Huang, Y. Tong, and X. Jiang. 2020. Urolithin B improves cardiac function and reduces susceptibility to ventricular arrhythmias in rats after myocardial infarction. European Journal of Pharmacology 871 (2020):172936. doi: 10.1016/j.ejphar.2020.172936.
   PubMedGoogle Scholar
• Ghosh, N., A. Das, N. Biswas, S. Gnyawali, K. Singh, M. Gorain, C. Polcyn, S. Khanna, S. Roy, and C. K. Sen. 2020. Urolithin A augments angiogenic pathways in skeletal muscle by bolstering NAD + and SIRT1. Scientific Reports 10 (1):1–13. doi: 10.1038/s41598-020-76564-7.
   PubMed Web of Science ®Google Scholar
• Giménez-Bastida, J. A., M. A. Ávila-Gálvez, J. C. Espín, and A. González-Sarrías. 2020. The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells. Food and Chemical Toxicology 139 (2020):111260–10. doi: 10.1016/j.fct.2020.111260.
   PubMedGoogle Scholar
• Giménez-Bastida, J. A., A. Gonzalez-Sarrias, M. Larrosa, F. Tomas-Barberan, J. C. Espin, and M. T. Garcia-Conesa. 2012. Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-alpha-induced inflammation and associated molecular markers in human aortic endothelial cells. Molecular Nutrition & Food Research 56 (5):784–96. doi: 10.1002/mnfr.201100677.
   PubMed Web of Science ®Google Scholar
• Giorgio, C., P. Mena, D. Del Rio, F. Brighenti, E. Barocelli, I. Hassan Mohamed, D. Callegari, A. Lodola, and M. Tognolini. 2015. The ellagitannin colonic metabolite urolithin D selectively inhibits Epha2 phosphorylation in prostate cancer cells. Molecular Nutrition & Food Research 59 (11):2155–67. doi: 10.1002/mnfr.201500470.
   PubMed Web of Science ®Google Scholar
• Gong, Z., J. Huang, B. Xu, Z. Ou, L. Zhang, X. Lin, X. Ye, X. Kong, D. Long, X. Sun, et al. 2019. Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice. Journal of Neuroinflammation 16 (1):1–13. doi: 10.1186/s12974-019-1450-3.
   PubMedGoogle Scholar
• González-Sarrías, A., V. Miguel, G. Merino, R. Lucas, J. C. Morales, F. Tomás-Barberán, A. I. Alvarez, and J. C. Espín. 2013. The gut microbiota ellagic acid-derived metabolite urolithin A and its sulfate conjugate are substrates for the drug efflux transporter breast cancer resistance protein (ABCG2/BCRP). Journal of Agricultural and Food Chemistry 61 (18):4352–9. doi: 10.1021/jf4007505.
   PubMed Web of Science ®Google Scholar
• González-Sarrías, A., M. Á. Núñez-Sánchez, R. García-Villalba, F. A. Tomás-Barberán, and J. C. Espín. 2017. Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin A isomer: the role of cell metabolism. European Journal of Nutrition 56 (2):831–41. doi: 10.1007/s00394-015-1131-7.
   PubMed Web of Science ®Google Scholar
• González-Sarrias, A., M. A. Nunez-Sanchez, J. Tome-Carneiro, F. A. Tomas-Barberan, M. T. Garcia-Conesa, and J. C. Espin. 2016. Comprehensive characterization of the effects of ellagic acid and urolithins on colorectal cancer and key-associated molecular hallmarks: microrna cell specific induction of CDKN1A (p21) as a common mechanism involved. Molecular Nutrition and Food Research 60 (4):701–16. doi: 10.1002/mnfr.201500780.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Sarrias, A., J. Tome-Carneiro, A. Bellesia, F. A. Tomas-Barberan, and J. C. Espin. 2015. The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells. Food & Function 6 (5):1460–9. doi: 10.1039/c5fo00120j.
   PubMed Web of Science ®Google Scholar
• Guada, M., R. Ganugula, M. Vadhanam, and M. N. V. Ravi Kumar. 2017. Urolithin A mitigates cisplatin-induced nephrotoxicity by inhibiting renal inflammation and apoptosis in an experimental rat model. The Journal of Pharmacology and Experimental Therapeutics 363 (1):58–65. doi: 10.1124/jpet.117.242420.
   PubMed Web of Science ®Google Scholar
• Gyawali, B., S. P. Hey, and A. S. Kesselheim. 2019. Assessment of the clinical benefit of cancer drugs receiving accelerated approval. JAMA Internal Medicine 179 (7):906–13. doi: 10.1001/jamainternmed.2019.0462.
   PubMed Web of Science ®Google Scholar
• Han, Q., D. Su, C. Shi, P. Liu, Y. Wang, B. Zhu, and X. Xia. 2020. Urolithin A attenuated ox-LDL-induced cholesterol accumulation in macrophages partly through regulating miR-33a and ERK/AMPK/SREBP1 signaling pathways. Food & Function 11 (4):3432–40. doi: 10.1039/C9FO02471A.
   PubMed Web of Science ®Google Scholar
• Han, Q. A., C. Yan, L. Wang, G. Li, Y. Xu, and X. Xia. 2016. Urolithin A attenuates ox-LDL-induced endothelial dysfunction partly by modulating microRNA-27 and ERK/PPAR-gamma pathway. Molecular Nutrition & Food Research 60 (9):1933–43. doi: 10.1002/mnfr.201500827.
   PubMed Web of Science ®Google Scholar
• Heilman, J., P. Andreux, N. Tran, C. Rinsch, and W. Blanco-Bose. 2017. Safety assessment of urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 108 (Pt A):289–97. doi: 10.1016/j.fct.2017.07.050.
   PubMedGoogle Scholar
• Hering, N. A., J. Luettig, B. Jebautzke, J. D. Schulzke, and R. Rosenthal. 2021. The punicalagin metabolites ellagic acid and urolithin A exert different strengthening and anti-inflammatory effects on tight junction-mediated intestinal barrier function in vitro. Frontiers in Pharmacology 12:610164. doi: 10.3389/fphar.2021.610164.
   PubMed Web of Science ®Google Scholar
• Hodgkinson, K., L. A. Forrest, N. Vuong, K. Garson, B. Djordjevic, and B. C. Vanderhyden. 2018. GREB1 is an estrogen receptor-regulated tumour promoter that is frequently expressed in ovarian cancer. Oncogene 37 (44):5873–86. doi: 10.1038/s41388-018-0377-y.
   PubMed Web of Science ®Google Scholar
• Ishimoto, H., M. Shibata, Y. Myojin, H. Ito, Y. Sugimoto, A. Tai, and T. Hatano. 2011. In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin A. Bioorganic & Medicinal Chemistry Letters 21 (19):5901–4. doi: 10.1016/j.bmcl.2011.07.086.
   PubMed Web of Science ®Google Scholar
• Ito, H. 2011. Metabolites of the ellagitannin geraniin and their antioxidant activities. Planta Medica 77 (11):1110–5. doi: 10.1055/s-0030-1270749.
   PubMed Web of Science ®Google Scholar
• Jing, T., J. Liao, K. Shen, X. Chen, Z. Xu, W. Tian, Y. Wang, B. Jin, and H. Pan. 2019. Protective effect of urolithin A on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 129:108–14. doi: 10.1016/j.fct.2019.04.031.
   PubMed Web of Science ®Google Scholar
• Kallio, T., J. Kallio, M. Jaakkola, M. Maki, P. Kilpelainen, and V. Virtanen. 2013. Urolithins display both antioxidant and pro-oxidant activities depending on assay system and conditions. Journal of Agricultural and Food Chemistry 61 (45):10720–9. doi: 10.1021/jf403208d.
   PubMed Web of Science ®Google Scholar
• Kang, I., Y. Kim, F. A. Tomas-Barberan, J. C. Espin, and S. Chung. 2016. Urolithin A, C, and D, but not iso-urolithin A and urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes. Molecular Nutrition & Food Research 60 (5):1129–38. doi: 10.1002/mnfr.201500796.
   PubMed Web of Science ®Google Scholar
• Kim, K. B., S. Lee, and J. H. Kim. 2020. Neuroprotective effects of urolithin A on H2O2-induced oxidative stress-mediated apoptosis in SK-N-MC cells. Nutrition Research and Practice 14 (1):3–11. doi: 10.4162/nrp.2020.
   PubMed Web of Science ®Google Scholar
• Kinney, J. W., S. M. Bemiller, A. S. Murtishaw, A. M. Leisgang, A. M. Salazar, and B. T. Lamb. 2018. Inflammation as a central mechanism in Alzheimer's disease. Alzheimer's & Dementia (New York, N. Y.) 4 (2018):575–90. doi: 10.1016/j.trci.2018.06.014.
   PubMedGoogle Scholar
• Komatsu, W., H. Kishi, K. Yagasaki, and S. Ohhira. 2018. Urolithin A attenuates pro-inflammatory mediator production by suppressing PI3-K/Akt/NF-kappaB and JNK/AP-1 signaling pathways in lipopolysaccharide-stimulated RAW264 macrophages: possible involvement of NADPH oxidase-derived reactive oxygen species. European Journal of Pharmacology 833 (2018):411–24. doi: 10.1016/j.ejphar.2018.06.023.
   PubMedGoogle Scholar
• Kujawska, M., M. Jourdes, M. Kurpik, M. Szulc, H. Szaefer, P. Chmielarz, G. Kreiner, V. Krajka-Kuźniak, P. Ł. Mikołajczak, P.-L. Teissedre, et al. 2019. Neuroprotective effects of pomegranate juice against Parkinson's disease and presence of ellagitannins-derived metabolite-urolithin A in the brain. International Journal of Molecular Sciences 21 (1):202–20. doi: 10.3390/ijms21010202.
   PubMed Web of Science ®Google Scholar
• Lacas, B., J. Bourhis, J. Overgaard, Q. Zhang, V. Grégoire, M. Nankivell, B. Zackrisson, Z. Szutkowski, R. Suwiński, M. Poulsen, MARCH Collaborative Group, et al. 2017. Role of radiotherapy fractionation in head and neck cancers (March): an updated meta-analysis. The Lancet. Oncology 18 (9):1221–37. doi: 10.1016/S1470-2045(17)30458-8.
   PubMed Web of Science ®Google Scholar
• Lall, N. 2018. Medicinal plants for holistic health and well-being. London, United Kingdom: Academic Press, an Imprint of Elsevier.
   Google Scholar
• Larrosa, M., A. Gonzalez-Sarrias, M. J. Yanez-Gascon, M. V. Selma, M. Azorin-Ortuno, S. Toti, F. Tomas-Barberan, P. Dolara, and J. C. Espin. 2010. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. The Journal of Nutritional Biochemistry 21 (8):717–25. doi: 10.1016/j.jnutbio.2009.04.012.
   PubMed Web of Science ®Google Scholar
• Larsson, L., H. Degens, M. Li, L. Salviati, Y. I. Lee, W. Thompson, J. L. Kirkland, and M. Sandri. 2019. Sarcopenia: aging-related loss of muscle mass and function. Physiological Reviews 99 (1):427–511. doi: 10.1152/physrev.00061.2017.
   PubMed Web of Science ®Google Scholar
• Lee, G., J. S. Park, E. J. Lee, J. H. Ahn, and H. S. Kim. 2019. Anti-inflammatory and antioxidant mechanisms of urolithin B in activated microglia. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 55 (2018):50–7. doi: 10.1016/j.phymed.2018.06.032.
   PubMedGoogle Scholar
• Lee, H. J., Y. H. Jung, G. E. Choi, J. S. Kim, C. W. Chae, J. R. Lim, S. Y. Kim, J. H. Yoon, J. H. Cho, S.-J. Lee, et al. 2021. Urolithin A suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis. Cell Death and Differentiation 28 (1):184–202. doi: 10.1038/s41418-020-0593-1.
   PubMed Web of Science ®Google Scholar
• Les, F., J. M. Arbones-Mainar, M. S. Valero, and V. Lopez. 2018. Pomegranate polyphenols and urolithin A inhibit alpha-glucosidase, dipeptidyl peptidase-4, lipase, triglyceride accumulation and adipogenesis related genes in 3T3-L1 adipocyte-like cells. Journal of Ethnopharmacology 220 (2018):67–74. doi: 10.1016/j.jep.2018.03.029.
   PubMedGoogle Scholar
• Li, B. Y., X. Y. Xu, R. Y. Gan, Q. C. Sun, J. M. Meng, A. Shang, Q. Q. Mao, and H. B. Li. 2019. Targeting gut microbiota for the prevention and management of diabetes mellitus by dietary natural products. Foods 8 (10):440–18. doi: 10.3390/foods8100440.
   PubMed Web of Science ®Google Scholar
• Li, Q., K. Li, Z. Chen, and B. Zhou. 2020. Anti-renal fibrosis and anti-inflammation effect of urolithin B, ellagitannin-gut microbial-derived metabolites in unilateral ureteral obstruction rats. Journal of Functional Foods 65 (2020):103748–13. doi: 10.1016/j.jff.2019.103748.
   Google Scholar
• Liberal, J., A. Carmo, C. Gomes, M. T. Cruz, and M. T. Batista. 2017. Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells. Investigational New Drugs 35 (6):671–81. doi: 10.1007/s10637-017-0483-7.
   PubMed Web of Science ®Google Scholar
• Lin, J., J. Zhuge, X. Zheng, Y. Wu, Z. Zhang, T. Xu, Z. Meftah, H. Xu, Y. Wu, N. Tian, et al. 2020a. Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway. Free Radical Biology & Medicine 150 (2020):109–19. doi: 10.1016/j.freeradbiomed.2020.02.024.
   PubMedGoogle Scholar
• Lin, X.-H., X.-J. Ye, Q.-F. Li, Z. Gong, X. Cao, J.-H. Li, S.-T. Zhao, X.-D. Sun, X.-S. He, and A.-G. Xuan. 2020b. Urolithin A prevents focal cerebral ischemic injury via attenuating apoptosis and neuroinflammation in mice. Neuroscience 448 (2020):94–106. doi: 10.1016/j.neuroscience.2020.09.027.
   PubMedGoogle Scholar
• Liu, C. F., X. L. Li, Z. L. Zhang, L. Qiu, S. X. Ding, J. X. Xue, G. P. Zhao, and J. Li. 2019. Antiaging effects of urolithin A on replicative senescent human skin fibroblasts. Rejuvenation Research 22 (3):191–200. doi: 10.1089/rej.2018.2066.
   PubMed Web of Science ®Google Scholar
• Liu, H., H. Kang, C. Song, Z. Lei, L. Li, J. Guo, Y. Xu, H. Guan, Z. Fang, and F. Li. 2018. Urolithin A inhibits the catabolic effect of TNF-alpha on nucleus pulposus cell and alleviates intervertebral disc degeneration in vivo. Frontiers in Pharmacology 9:1043:1–11. doi: 10.3389/fphar.2018.01043.
   Web of Science ®Google Scholar
• Livingston, S., S. Mallick, D. A. Lucas, M. S. Sabir, Z. L. Sabir, H. Purdin, S. Nidamanuri, C. A. Haussler, M. R. Haussler, and P. W. Jurutka. 2020. Pomegranate derivative urolithin A enhances vitamin D receptor signaling to amplify serotonin-related gene induction by 1,25-dihydroxyvitamin D. Biochemistry and Biophysics Reports 24 (2020):100825–11. doi: 10.1016/j.bbrep.2020.100825.
   PubMedGoogle Scholar
• Lv, M., C. Shi, F. Pan, J. Shao, L. Feng, G. Chen, C. Ou, J. Zhang, and W. Fu. 2019. Urolithin B suppresses tumor growth in hepatocellular carcinoma through inducing the inactivation of Wnt/catenin signaling. Journal of Cellular Biochemistry 120 (10):17273–82. doi: 10.1002/jcb.28989.
   PubMed Web of Science ®Google Scholar
• Loos, R. J. F, and G. S. H. Yeo. 2022. The genetics of obesity: from discovery to biology. Nature Reviews. Genetics 23 (2):120–33. doi: 10.1038/s41576-021-00414-z.
   PubMed Web of Science ®Google Scholar
• Luo, M., R. Y. Gan, B. Y. Li, Q. Q. Mao, A. Shang, X. Y. Xu, H. Y. Li, and H. B. Li. 2021. Effects and mechanisms of tea on Parkinson’s disease, Alzheimer’s disease and depression. Food Reviews International 2021:1–29. doi: 10.1080/87559129.2021.1904413.
   Google Scholar
• Manigandan, S, and J. W. Yun. 2020. Urolithin A induces brown-like phenotype in 3T3-L1 white adipocytes via β3-adrenergic receptor-p38 MAPK signaling pathway. Biotechnology and Bioprocess Engineering 25 (3):345–55. doi: 10.1007/s12257-020-0149-8.
   Web of Science ®Google Scholar
• Mathijssen, R. H., A. Sparreboom, and J. Verweij. 2014. Determining the optimal dose in the development of anticancer agents. Nature Reviews. Clinical Oncology 11 (5):272–81. doi: 10.1038/nrclinonc.2014.40.
   PubMed Web of Science ®Google Scholar
• Muku, G. E., I. A. Murray, J. C. Espin, and G. H. Perdew. 2018. Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonist. Metabolites 8 (4):86–18. doi: 10.3390/metabo8040086.
   PubMed Web of Science ®Google Scholar
• Nagai, H, and Y. H. Kim. 2017. Cancer prevention from the perspective of global cancer burden patterns. Journal of Thoracic Disease 9 (3):448–51. doi: 10.21037/jtd.2017.02.75.
   PubMed Web of Science ®Google Scholar
• Newman, D. J, and G. M. Cragg. 2020. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products 83 (3):770–803. doi: 10.1021/acs.jnatprod.9b01285.
   PubMed Web of Science ®Google Scholar
• Norden, E, and E. H. Heiss. 2019. Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells. Carcinogenesis 40 (1):93–101. doi: 10.1093/carcin/bgy158.
   PubMed Web of Science ®Google Scholar
• Núñez-Sánchez, M. Á., A. Karmokar, A. González-Sarrías, R. García-Villalba, F. A. Tomás-Barberán, M. T. García-Conesa, K. Brown, and J. C. Espín. 2016. In vivo relevant mixed urolithins and ellagic acid inhibit phenotypic and molecular colon cancer stem cell features: a new potentiality for ellagitannin metabolites against cancer. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 92 (2016):8–16. doi: 10.1016/j.fct.2016.03.011.
   PubMedGoogle Scholar
• Piwowarski, J. P., A. K. Kiss, S. Granica, and T. Moeslinger. 2015. Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit lps-induced inflammation in RAW 264.7 murine macrophages. Molecular Nutrition & Food Research 59 (11):2168–77. doi: 10.1002/mnfr.201500264.
   PubMed Web of Science ®Google Scholar
• Qiu, Z., B. Zhou, L. Jin, H. Yu, L. Liu, Y. Liu, C. Qin, S. Xie, and F. Zhu. 2013. In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 59 (2013):428–37. doi: 10.1016/j.fct.2013.06.025.
   PubMedGoogle Scholar
• Qiu, Z., J. Zhou, C. Zhang, Y. Cheng, J. Hu, and G. Zheng. 2018. Antiproliferative effect of urolithin A, the ellagic acid-derived colonic metabolite, on hepatocellular carcinoma HepG2.2.15 cells by targeting Lin28a/let-7a axis. Brazilian Journal of Medical and Biological Research 51 (7):1–8. doi: 10.1590/1414-431x20187220.
   Web of Science ®Google Scholar
• Reach, G., V. Pechtner, R. Gentilella, A. Corcos, and A. Ceriello. 2017. Clinical inertia and its impact on treatment intensification in people with type 2 diabetes mellitus. Diabetes & Metabolism 43 (6):501–11. doi: 10.1016/j.diabet.2017.06.003.
   PubMed Web of Science ®Google Scholar
• Ren, J., N. N. Wu, S. Wang, J. R. Sowers, and Y. Zhang. 2021. Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications. Physiological Reviews 101 (4):1745–807. doi: 10.1152/physrev.00030.2020.
   PubMed Web of Science ®Google Scholar
• Reuter, S., S. C. Gupta, M. M. Chaturvedi, and B. B. Aggarwal. 2010. Oxidative stress, inflammation, and cancer: how are they linked? Free Radical Biology & Medicine 49 (11):1603–16. doi: 10.1016/j.freeradbiomed.2010.09.006.
   PubMed Web of Science ®Google Scholar
• Rodriguez, J., N. Pierre, D. Naslain, F. Bontemps, D. Ferreira, F. Priem, L. Deldicque, and M. Francaux. 2017. Urolithin B, a newly identified regulator of skeletal muscle mass. Journal of Cachexia, Sarcopenia and Muscle 8 (4):583–97. doi: 10.1002/jcsm.12190.
   PubMed Web of Science ®Google Scholar
• Roessner, A., D. Kuester, P. Malfertheiner, and R. Schneider-Stock. 2008. Oxidative stress in ulcerative colitis-associated carcinogenesis. Pathology, Research and Practice 204 (7):511–24. doi: 10.1016/j.prp.2008.04.011.
   PubMed Web of Science ®Google Scholar
• Rubinsztein, D. C., G. Marino, and G. Kroemer. 2011. Autophagy and aging. Cell 146 (5):682–95. doi: 10.1016/j.cell.2011.07.030.
   PubMed Web of Science ®Google Scholar
• Rudno-Rudzińska, J., W. Kielan, E. Frejlich, K. Kotulski, W. Hap, K. Kurnol, P. Dzierżek, M. Zawadzki, and A. Hałoń. 2017. A review on Eph/ephrin, angiogenesis and lymphangiogenesis in gastric, colorectal and pancreatic cancers. Chinese Journal of Cancer Research = Chung-Kuo Yen Cheng Yen Chiu 29 (4):303–12. doi: 10.21147/j.issn.1000-9604.2017.04.03.
   PubMed Web of Science ®Google Scholar
• Rupiani, S., L. Guidotti, M. Manerba, L. D. Ianni, E. Giacomini, F. Falchi, G. D. Stefano, M. Roberti, and M. Recanatini. 2016. Synthesis of natural urolithin M6, a galloflavin mimetic, as a potential inhibitor of lactate dehydrogenase A. Organic & Biomolecular Chemistry 14 (46):10981–7. doi: 10.1039/C6OB01977C.
   PubMed Web of Science ®Google Scholar
• Ryu, D., L. Mouchiroud, P. A. Andreux, E. Katsyuba, N. Moullan, A. A. Nicolet-Dit-Felix, E. G. Williams, P. Jha, G. Lo Sasso, D. Huzard, et al. 2016. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine 22 (8):879–88. doi: 10.1038/nm.4132.
   PubMed Web of Science ®Google Scholar
• Saha, P., B. S. Yeoh, R. Singh, B. Chandrasekar, P. K. Vemula, B. Haribabu, M. Vijay-Kumar, and V. R. Jala. 2016. Gut microbiota conversion of dietary ellagic acid into bioactive phytoceutical urolithin A inhibits heme peroxidases. PLoS One 11 (6):e0156811–21. doi: 10.1371/journal.pone.0156811.
   PubMed Web of Science ®Google Scholar
• Sala, R., P. Mena, M. Savi, F. Brighenti, A. Crozier, M. Miragoli, D. Stilli, and D. Del Rio. 2015. Urolithins at physiological concentrations affect the levels of pro-inflammatory cytokines and growth factor in cultured cardiac cells in hyperglucidic conditions. Journal of Functional Foods 15 (2015):97–105. doi: 10.1016/j.jff.2015.03.019.
   Google Scholar
• Saleem, Y. I. M., H. Albassam, and M. Selim. 2020. Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner. European Journal of Nutrition 59 (4):1607–18. doi: 10.1007/s00394-019-02016-2.
   PubMed Web of Science ®Google Scholar
• Sánchez-González, C., C. J. Ciudad, V. Noé, and M. Izquierdo-Pulido. 2014. Walnut polyphenol metabolites, urolithins A and B, inhibit the expression of the prostate-specific antigen and the androgen receptor in prostate cancer cells. Food & Function 5 (11):2922–30. doi: 10.1039/C4FO00542B.
   PubMed Web of Science ®Google Scholar
• Sanchez-Gonzalez, C., C. J. Ciudad, M. Izquierdo-Pulido, and V. Noe. 2016. Urolithin A causes p21 up-regulation in prostate cancer cells. European Journal of Nutrition 55 (3):1099–112. doi: 10.1007/s00394-015-0924-z.
   PubMed Web of Science ®Google Scholar
• Savi, M., L. Bocchi, L. Bresciani, A. Falco, F. Quaini, P. Mena, F. Brighenti, A. Crozier, D. Stilli, and D. Del Rio. 2018. Trimethylamine-N-oxide (TMAO)-induced impairment of cardiomyocyte function and the protective role of urolithin B-glucuronide. Molecules 23 (3):549–12. doi: 10.3390/molecules23030549.
   PubMed Web of Science ®Google Scholar
• Savi, M., L. Bocchi, P. Mena, M. Dall’Asta, A. Crozier, F. Brighenti, D. Stilli, and D. Del Rio. 2017. In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats. Cardiovascular Diabetology 16 (1):1–13. doi: 10.1186/s12933-017-0561-3.
   PubMedGoogle Scholar
• Seeram, N. P., S. M. Henning, Y. Zhang, M. Suchard, Z. Li, and D. Heber. 2006. Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. The Journal of Nutrition 136 (10):2481–5. doi: 10.1093/jn/136.10.2481. PMID: 16988113.
   PubMed Web of Science ®Google Scholar
• Sekar, D., R. Krishnan, M. Panagal, P. Sivakumar, V. Gopinath, and V. Basam. 2016. Deciphering the role of microRNA 21 in cancer stem cells (CSCs). Genes & Diseases 3 (4):277–81. doi: 10.1016/j.gendis.2016.05.002.
   PubMedGoogle Scholar
• Selma, M. V., D. Beltran, R. Garcia-Villalba, J. C. Espin, and F. A. Tomas-Barberan. 2014a. Description of urolithin production capacity from ellagic acid of two human intestinal gordonibacter species. Food & Function 5 (8):1779–84. doi: 10.1039/c4fo00092g.
   PubMed Web of Science ®Google Scholar
• Selma, M. V., M. Romo-Vaquero, R. García-Villalba, A. González-Sarrías, F. A. Tomás-Barberán, and J. C. Espín. 2016. The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism. Food & Function 7 (4):1769–74. doi: 10.1039/c5fo01100k.
   PubMed Web of Science ®Google Scholar
• Selma, M. V., F. A. Tomas-Barberan, D. Beltran, R. Garcia-Villalba, and J. C. Espin. 2014b. Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut. International Journal of Systematic and Evolutionary Microbiology 64 (Pt 7):2346–52. doi: 10.1099/ijs.0.055095-0.
   PubMedGoogle Scholar
• Seravalle, G, and G. Grassi. 2017. Obesity and hypertension. Pharmacological Research 122 (2017):1–7. doi: 10.1016/j.phrs.2017.05.013.
   PubMedGoogle Scholar
• Shang, A., R. Y. Gan, X. Y. Xu, Q. Q. Mao, P. Z. Zhang, and H. B. Li. 2021. Effects and mechanisms of edible and medicinal plants on obesity: an updated review. Critical Reviews in Food Science and Nutrition 61 (12):2061–77. doi: 10.1080/10408398.2020.1769548.
   PubMed Web of Science ®Google Scholar
• Shang, A., H. Y. Liu, M. Luo, Y. Xia, X. Yang, H. Y. Li, D. T. Wu, Q. Sun, F. Geng, H. B. Li, et al. 2022. Sweet tea (Lithocarpus polystachyus rehd.) as a new natural source of bioactive dihydrochalcones with multiple health benefits. Critical Reviews in Food Science and Nutrition 62 (4):917–34. doi: 10.1080/10408398.2020.1830363.
   PubMed Web of Science ®Google Scholar
• Sharma, M., L. Li, J. Celver, C. Killian, A. Kovoor, and N. P. Seeram. 2010. Effects of fruit ellagitannin extracts, ellagic acid, and their colonic metabolite, urolithin A, on wnt signaling. Journal of Agricultural and Food Chemistry 58 (7):3965–9. doi: 10.1021/jf902857v.
   PubMed Web of Science ®Google Scholar
• Shen, P.-X., X. Li, S.-Y. Deng, L. Zhao, Y.-Y. Zhang, X. Deng, B. Han, J. Yu, Y. Li, Z.-Z. Wang, et al. 2021. Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor. EBioMedicine 64 (2021):103227–13. doi: 10.1016/j.ebiom.2021.103227.
   PubMedGoogle Scholar
• Shukur, K. T., T. Ercetin, C. Luise, W. Sippl, O. Sirkecioglu, M. Ulgen, G. P. Coskun, M. Yarim, M. Gazi, and H. O. Gulcan. 2021. Design, synthesis, and biological evaluation of new urolithin amides as multitarget agents against Alzheimer’s disease. Archiv Der Pharmazie 354 (5):2000467–11. doi: 10.1002/ardp.202000467.
   Web of Science ®Google Scholar
• Singh, R., S. Chandrashekharappa, P. K. Vemula, B. Haribabu, and V. R. Jala. 2020. Microbial metabolite urolithin B inhibits recombinant human monoamine oxidase A enzyme. Metabolites 10 (6):258–7. doi: 10.3390/metabo10060258.
   PubMed Web of Science ®Google Scholar
• Spigoni, V., P. Mena, M. Cito, F. Fantuzzi, R. C. Bonadonna, F. Brighenti, A. D. Cas, and D. Del Rio. 2016. Effects on nitric oxide production of urolithins, gut-derived ellagitannin metabolites, in human aortic endothelial cells. Molecules 21 (8):1009–13. doi: 10.3390/molecules21081009.
   PubMed Web of Science ®Google Scholar
• Stanisławska, I. J., S. Granica, J. P. Piwowarski, J. Szawkało, K. Wiązecki, Z. Czarnocki, and A. K. Kiss. 2019. The activity of urolithin A and M4 valerolactone, colonic microbiota metabolites of polyphenols, in a prostate cancer in vitro model. Planta Medica 85 (2):118–25. doi: 10.1055/a-0755-7715.
   PubMed Web of Science ®Google Scholar
• Stohs, S. J, and V. Badmaev. 2016. A review of natural stimulant and non-stimulant thermogenic agents. Phytotherapy Research: PTR 30 (5):732–40. doi: 10.1002/ptr.5583.
   PubMed Web of Science ®Google Scholar
• Stolarczyk, M., J. P. Piwowarski, S. Granica, J. Stefańska, M. Naruszewicz, and A. K. Kiss. 2013. Extracts from Epilobium sp. herbs, their components and gut microbiota metabolites of epilobium ellagitannins, urolithins, inhibit hormone-dependent prostate cancer cells-(LNCaP) proliferation and PSA secretion: effect of epilobium on prostate cells proliferation and PSA secretion. Phytotherapy Research: PTR 27 (12):1842–8. doi: 10.1002/ptr.4941.
   PubMed Web of Science ®Google Scholar
• Tang, L., Y. Mo, Y. Li, Y. Zhong, S. He, Y. Zhang, Y. Tang, S. Fu, X. Wang, and A. Chen. 2017. Urolithin A alleviates myocardial ischemia/reperfusion injury via PI3K/Akt pathway. Biochemical and Biophysical Research Communications 486 (3):774–80. doi: 10.1016/j.bbrc.2017.03.119.
   PubMed Web of Science ®Google Scholar
• Tao, J., S. Li, R. Y. Gan, C. N. Zhao, X. Meng, and H. B. Li. 2020. Targeting gut microbiota with dietary components on cancer: effects and potential mechanisms of action. Critical Reviews in Food Science and Nutrition 60 (6):1025–37. doi: 10.1080/10408398.2018.1555789.
   PubMed Web of Science ®Google Scholar
• Toney, A. M., R. Fan, Y. Xian, V. Chaidez, A. E. Ramer-Tait, and S. Chung. 2019. Urolithin A, a gut metabolite, improves insulin sensitivity through augmentation of mitochondrial function and biogenesis. Obesity (Silver Spring, Md.) 27 (4):612–20. doi: 10.1002/oby.22404.
   PubMed Web of Science ®Google Scholar
• Toney, A. M., M. Albusharif, D. Works, L. Polenz, S. Schlange, V. Chaidez, A. E. Ramer-Tait, and S. Chung. 2020. Differential effects of whole red raspberry polyphenols and their gut metabolite urolithin A on neuroinflammation in BV-2 microglia. International Journal of Environmental Research and Public Health 18 (1):68–11. doi: 10.3390/ijerph18010068.
   PubMed Web of Science ®Google Scholar
• Totiger, T. M., S. Srinivasan, V. R. Jala, P. Lamichhane, A. R. Dosch, A. A. Gaidarski, C. Joshi, S. Rangappa, J. Castellanos, P. K. Vemula, et al. 2019. Urolithin A, a novel natural compound to target PI3K/AKT/mTOR pathway in pancreatic cancer. Molecular Cancer Therapeutics 18 (2):301–11. doi: 10.1158/1535-7163.MCT-18-0464.
   PubMed Web of Science ®Google Scholar
• Toubal, S., C. Oiry, M. Bayle, G. Cros, and J. Neasta. 2020. Urolithin C increases glucose-induced ERK activation which contributes to insulin secretion. Fundamental & Clinical Pharmacology 34 (5):571–80. doi: 10.1111/fcp.12551.
   PubMed Web of Science ®Google Scholar
• Tuohetaerbaike, B., Y. Zhang, Y. Tian, N. N. Zhang, J. Kang, X. Mao, Y. Zhang, and X. Li. 2020. Pancreas protective effects of urolithin A on type 2 diabetic mice induced by high fat and streptozotocin via regulating autophagy and AKT/mTOR signaling pathway. Journal of Ethnopharmacology 250 (2020):112479. doi: 10.1016/j.jep.2019.112479.
   PubMedGoogle Scholar
• Velagapudi, R., I. Lepiarz, A. El-Bakoush, F. O. Katola, H. Bhatia, B. L. Fiebich, and O. A. Olajide. 2019. 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. Molecular Nutrition & Food Research 63 (10):1801237. doi: 10.1002/mnfr.201801237.
   Web of Science ®Google Scholar
• Vicinanza, R., Y. Zhang, S. M. Henning, and D. Heber. 2013. Pomegranate juice metabolites, ellagic acid and urolithin A, synergistically inhibit androgen-independent prostate cancer cell growth via distinct effects on cell cycle control and apoptosis. Evidence-Based Complementary and Alternative Medicine: eCAM 2013 (10):247504–12. doi: 10.1155/2013/247504.
   PubMedGoogle Scholar
• Wagner, A. D., N. L. Syn, M. Moehler, W. Grothe, W. P. Yong, B. C. Tai, J. Ho, and S. Unverzagt. 2017. Chemotherapy for advanced gastric cancer. The Cochrane Database of Systematic Reviews 8 (8):CD004064–219. doi: 10.1002/14651858.CD004064.pub4.
   PubMedGoogle Scholar
• Wang, S. T., W. C. Chang, C. Hsu, and N. W. Su. 2017. Antimelanogenic effect of urolithin A and urolithin B the colonic metabolites of ellagic acid, in b16 melanoma cells. Journal of Agricultural and Food Chemistry 65 (32):6870–6. doi: 10.1021/acs.jafc.7b02442.
   PubMed Web of Science ®Google Scholar
• Wang, Y., H. Huang, Y. Jin, K. Shen, X. Chen, Z. Xu, B. Jin, and H. Pan. 2019. Role of TFEB in autophagic modulation of ischemia reperfusion injury in mice kidney and protection by urolithin A. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 131 (2019):110591. doi: 10.1016/j.fct.2019.110591.
   PubMedGoogle Scholar
• Wang, Y., Z. Qiu, B. Zhou, C. Liu, J. Ruan, Q. Yan, J. Liao, and F. Zhu. 2015. In vitro antiproliferative and antioxidant effects of ­urolithin A, the colonic metabolite of ellagic acid, on hepatocellular carcinomas HepG2 cells. Toxicology in Vitro: An International Journal Published in Association with BIBRA 29 (5):1107–15. doi: 10.1016/j.tiv.2015.04.008.
   PubMed Web of Science ®Google Scholar
• Xia, B., X. C. Shi, B. C. Xie, M. Q. Zhu, Y. Chen, X. Y. Chu, G. H. Cai, M. Liu, S. Z. Yang, G. A. Mitchell, et al. 2020. Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice. PLoS Biology 18 (3):e3000688–26. doi: 10.1371/journal.pbio.3000688.
   PubMed Web of Science ®Google Scholar
• Xu, J., C. Yuan, G. Wang, J. Luo, H. Ma, L. Xu, Y. Mu, Y. Li, N. P. Seeram, X. Huang, et al. 2018. Urolithins attenuate LPS-induced neuroinflammation in BV2 microglia via MAPK, Akt, and NF-κB signaling pathways. Journal of Agricultural and Food Chemistry 66 (3):571–80. doi: 10.1021/acs.jafc.7b03285.
   PubMed Web of Science ®Google Scholar
• Xu, X. Y., C. N. Zhao, S. Y. Cao, G. Y. Tang, R. Y. Gan, and H. B. Li. 2020. Effects and mechanisms of tea for the prevention and management of cancers: an updated review. Critical Reviews in Food Science and Nutrition 60 (10):1693–705. doi: 10.1080/10408398.2019.1588223.
   PubMed Web of Science ®Google Scholar
• Xu, X. Y., C. N. Zhao, B. Y. Li, G. Y. Tang, A. Shang, R. Y. Gan, Y. B. Feng, and H. B. Li. 2021. Effects and mechanisms of tea on obesity. Critical Reviews in Food Science and Nutrition 1–18. doi: 10.1080/10408398.2021.1992748.
   Google Scholar
• Yang, J., Y. Guo, S. M. Henning, B. Chan, J. Long, J. Zhong, R. Acin-Perez, A. Petcherski, O. Shirihai, D. Heber, et al. 2020. Ellagic acid and its microbial metabolite urolithin A alleviate diet-induced insulin resistance in mice. Molecular Nutrition and Food Research 64 (19):1–17. doi: 10.1002/mnfr.202000091.
   Web of Science ®Google Scholar
• Yao, X., K. Panichpisal, N. Kurtzman, and K. Nugent. 2007. Cisplatin nephrotoxicity: a review. The American Journal of the Medical Sciences 334 (2):115–24. doi: 10.1097/MAJ.0b013e31812dfe1e.
   PubMed Web of Science ®Google Scholar
• Yin, P., J. Zhang, L. Yan, L. Yang, L. Sun, L. Shi, C. Ma, and Y. Liu. 2017. Urolithin C, a gut metabolite of ellagic acid, induces apoptosis in PC12 cells through a mitochondria-mediated pathway. RSC Advances 7 (28):17254–63. doi: 10.1039/C7RA01548H.
   Web of Science ®Google Scholar
• Yuan, T., H. Ma, W. Liu, D. B. Niesen, N. Shah, R. Crews, K. N. Rose, D. A. Vattem, and N. P. Seeram. 2016. Pomegranate’s neuroprotective effects against Alzheimer’s disease are mediated by urolithins, its ellagitannin-gut microbial derived metabolites. ACS Chemical Neuroscience 7 (1):26–33. doi: 10.1021/acschemneuro.5b00260.
   PubMed Web of Science ®Google Scholar
• Zhang, W., J. H. Chen, I. Aguilera-Barrantes, C. W. Shiau, X. Sheng, L. S. Wang, G. D. Stoner, and Y. W. Huang. 2016. Urolithin A suppresses the proliferation of endometrial cancer cells by mediating estrogen receptor-alpha-dependent gene expression. Molecular Nutrition & Food Research 60 (11):2387–95. doi: 10.1002/mnfr.201600048.
   PubMed Web of Science ®Google Scholar
• Zhang, S., T. Al-Maghout, H. Cao, L. Pelzl, M. S. Salker, M. Veldhoen, A. Cheng, F. Lang, and Y. Singh. 2019. Gut bacterial metabolite urolithin A (UA) mitigates Ca2+ entry in T cells by regulating miR-10a-5p. Frontiers in Immunology 10:1921. doi: 10.3389/fimmu.2019.01737.
   PubMed Web of Science ®Google Scholar
• Zhang, Y., Y. Zhang, G. Halemahebai, L. Tian, H. Dong, and G. Aisker. 2021. Urolithin A, a pomegranate metabolite, protects pancreatic β cells from apoptosis by activating autophagy. Journal of Ethnopharmacology 272 (2021):113628–0. doi: 10.1016/j.jep.2020.113628.
   PubMedGoogle Scholar
• Zhao, C., B. Liu, S. Piao, X. Wang, D. B. Lobell, Y. Huang, M. Huang, Y. Yao, S. Bassu, P. Ciais, et al. 2017. Temperature increase reduces global yields of major crops in four independent estimates. Proceedings of the National Academy of Sciences of the United States of America 114 (35):9326–31. doi: 10.1073/pnas.1701762114.
   PubMed Web of Science ®Google Scholar
• Zhao, R., X. Long, J. Yang, L. Du, X. Zhang, J. Li, and C. Hou. 2019. Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet. Food & Function 10 (12):8273–85. doi: 10.1039/C9FO02077B.
   PubMed Web of Science ®Google Scholar
• Zhou, B., J. Wang, G. Zheng, and Z. Qiu. 2016. Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 97 (2016):375–84. doi: 10.1016/j.fct.2016.10.005.
   PubMedGoogle Scholar
• Zhou, D. D., M. Luo, S. Y. Huang, A. Saimaiti, A. Shang, R. Y. Gan, and H. B. Li. 2021a. Effects and mechanisms of resveratrol on aging and age-related diseases. Oxidative Medicine and Cellular Longevity 2021:9932218–5. doi: 10.1155/2021/9932218.
   PubMed Web of Science ®Google Scholar
• Zhou, D. D., M. Luo, A. Shang, Q. Q. Mao, B. Y. Li, R. Y. Gan, and H. B. Li. 2021b. Antioxidant food components for the prevention and treatment of cardiovascular diseases: effects, mechanisms, and clinical studies. Oxidative Medicine and Cellular Longevity 2021:6627355–17. doi: 10.1155/2021/6627355.
   PubMed Web of Science ®Google Scholar
• Zhou, J., C. Zhang, G. H. Zheng, and Z. Qiu. 2018. Emblic leafflower (Phyllanthus emblica L.) fruits ameliorate vascular smooth muscle cell dysfunction in hyperglycemia: an underlying mechanism involved in ellagitannin metabolite urolithin A. Evidence-Based Complementary and Alternative Medicine: eCAM 2018:8478943–11. doi: 10.1155/2018/8478943.
   PubMed Web of Science ®Google Scholar
• Zou, D., R. Ganugula, M. Arora, M. B. Nabity, D. Sheikh-Hamad, and M. N. V. R. Kumar. 2019. Oral delivery of nanoparticle urolithin A normalizes cellular stress and improves survival in mouse model of cisplatin-induced AKI. American Journal of Physiology. Renal Physiology 317 (5):F1255–F1264. doi: 10.1152/ajprenal.00346.2019.
   PubMed Web of Science ®Google Scholar