Skip to content
2000
image of Innovative Therapeutic Potential of Herbal Extracts Containing Punicic and Ellagic Acid: Addressing Lower Urinary Tract Disorders

Abstract

This review highlights the new healing frontiers opened by herbal preparations rich in punicic acid, as well as ellagic acid, in the management of Lower Urinary Tract Disorders (LUTD). New data prove that these bioactive compounds possess strong anti-inflammatory, antioxidant, and antibacterial properties, and therefore, can be helpful in treating LUTD symptoms such as urgency, frequency, and dysuria. We conducted a comprehensive pharmacological assessment of punicic and ellagic acids aimed at determining their role in bladder health through modulation of inflammatory processes and both alteration and maintenance of urothelium integrity, in addition to obtaining some background information and chemical properties of these acids. Furthermore, we evaluated the findings of clinical and preclinical studies that demonstrated the ability of these formulations to improve the basic functions of the organs in the urinary system and the quality of life of patients. The review also reflects on the use of herbal extracts in combination with current therapies as a synergistic approach, particularly on the healing effects of such combinations and the need for solid clinical evidence to support such claims. This paper focuses on the concept of how LUTDs can be treated safely and effectively without the help of drugs by integrating modern scientific strategies with traditional approaches, which will thus increase the comprehensiveness of treatment in urological care. Future research should focus on improving how well these compounds are absorbed in the body and gathering long-term safety data, with the goal of incorporating them into treatment guidelines.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240378450250410073416
2025-05-02
2025-10-03

  • From This Site

    /content/journals/cmm/10.2174/0115665240378450250410073416
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Kheir G.B. Verbakel I. Wyndaele M. Monaghan T.F. Sinha S. Larsen T.H. Van Laecke E. Birder L. Hervé F. Everaert K. Lifelong LUTS: Understanding the bladder’s role and implications across transition phases, a comprehensive review. Neurourol. Urodyn. 2024 43 5 1066 1074 10.1002/nau.25304 38289317
    [Google Scholar]
  2. Ke Q.S. Lee C.L. Kuo H.C. Recurrent urinary tract infection in women and overactive bladder – Is there a relationship? Tzu-Chi Med. J. 2021 33 1 13 21 10.4103/tcmj.tcmj_38_20 33505873
    [Google Scholar]
  3. Medina M. Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther. Adv. Urol. 2019 11 1756287219832172 10.1177/1756287219832172 31105774
    [Google Scholar]
  4. Zhou Y. Zhou Z. Zheng L. Gong Z. Li Y. Jin Y. Huang Y. Chi M. Urinary tract infections caused by uropathogenic Escherichia coli: Mechanisms of infection and treatment options. Int. J. Mol. Sci. 2023 24 13 10537 10.3390/ijms241310537 37445714
    [Google Scholar]
  5. Bruxvoort K.J. Bider-Canfield Z. Casey J.A. Qian L. Pressman A. Liang A.S. Robinson S. Jacobsen S.J. Tartof S.Y. Outpatient urinary tract infections in an era of virtual healthcare: Trends from 2008 to 2017. Clin. Infect. Dis. 2020 71 1 100 108 10.1093/cid/ciz764 31437269
    [Google Scholar]
  6. Mortada E.M. Evidence-based complementary and alternative medicine in current medical practice. Cureus 2024 16 1 e52041 10.7759/cureus.52041 38344508
    [Google Scholar]
  7. McCann E. Sung A.H. Ye G. Vankeepuram L. Tabak Y.P. Contributing factors to the clinical and economic burden of patients with laboratory-confirmed carbapenem-nonsusceptible gram-negative urinary tract infections. Clinicoecon. Outcomes Res. 2020 12 191 200 10.2147/CEOR.S234840 32308447
    [Google Scholar]
  8. Pardeshi P. Prevalence of urinary tract infections and current scenario of antibiotic susceptibility pattern of bacteria causing UTI. Indian J Microbiol Res 2020 5 3 334 338 10.18231/2394‑5478.2018.0070
    [Google Scholar]
  9. Thompson J. Marijam A. Mitrani-Gold F.S. Wright J. Joshi A.V. Activity impairment, health-related quality of life, productivity, and self-reported resource use and associated costs of uncomplicated urinary tract infection among women in the United States. PLoS One 2023 18 2 e0277728 10.1371/journal.pone.0277728 36724152
    [Google Scholar]
  10. Eid A.M. Issa L. Arar K. Abu-Zant A. Makhloof M. Masarweh Y. Phytochemical screening, antioxidant, anti-diabetic, and anti-obesity activities, formulation, and characterization of a self-nanoemulsion system loaded with pomegranate (Punica granatum) seed oil. Sci. Rep. 2024 14 1 18841 10.1038/s41598‑024‑68476‑7 39138188
    [Google Scholar]
  11. Punicic acid. Available from: https://www.atamanchemicals.com/punicic-acid_u26479/
  12. Aruna P. Venkataramanamma D. Singh A.K. Singh R.P. Health benefits of punicic acid: A review. Compr. Rev. Food Sci. Food Saf. 2016 15 1 16 27 10.1111/1541‑4337.12171 33371578
    [Google Scholar]
  13. Valero-Mendoza A.G. Meléndez-Rentería N.P. Chávez-González M.L. Flores Gallegos A.C. Wong-Paz J.E. Govea-Salas M. Zugasti-Cruz A. Ascacio Valdés J.A. The whole pomegranate (Punica granatum L), biological properties and important findings: A review. Food Chem. Adv. 2023 2 100153 10.1016/j.focha.2022.100153
    [Google Scholar]
  14. Shabbir M.A. Khan M.R. Saeed M. Pasha I. Khalil A.A. Siraj N. Punicic acid: A striking health substance to combat metabolic syndromes in humans. Lipids Health Dis. 2017 16 1 99 10.1186/s12944‑017‑0489‑3 28558700
    [Google Scholar]
  15. Kang I. Buckner T. Shay N.F. Gu L. Chung S. Improvements in metabolic health with consumption of ellagic acid and subsequent conversion into urolithins: Evidence and mechanisms. Adv. Nutr. 2016 7 5 961 972 10.3945/an.116.012575 27633111
    [Google Scholar]
  16. Li J. Li S. Wang Y. Shang A. Functional, morphological and molecular characteristics in a novel rat model of spinal sacral nerve injury-surgical approach, pathological process and clinical relevance. Sci. Rep. 2022 12 1 10026 10.1038/s41598‑022‑13254‑6 35705577
    [Google Scholar]
  17. Zuccari G. Baldassari S. Ailuno G. Turrini F. Alfei S. Caviglioli G. Formulation strategies to improve oral bioavailability of ellagic acid. Appl. Sci. 2020 10 10 3353 10.3390/app10103353
    [Google Scholar]
  18. Vučić V. Grabež M. Trchounian A. Arsić A. Composition and potential health benefits of pomegranate: A review. Curr. Pharm. Des. 2019 25 16 1817 1827 10.2174/1381612825666190708183941 31298147
    [Google Scholar]
  19. Olszewska M.A. Gędas A. Simões M. Antimicrobial polyphenol-rich extracts: Applications and limitations in the food industry. Food Res. Int. 2020 134 109214 10.1016/j.foodres.2020.109214 32517896
    [Google Scholar]
  20. Carreno J.J. Tam I.M. Meyers J.L. Esterberg E. Candrilli S.D. Lodise T.P. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infect. Dis. 2020 7 1 ofz536 10.1093/ofid/ofz536 31951222
    [Google Scholar]
  21. Valentine-King M.A. Trautner B.W. Zoorob R.J. Germanos G. Hansen M. Salemi J.L. Gupta K. Grigoryan L. Analysis of recurrent urinary tract infection management in women seen in outpatient settings reveals opportunities for antibiotic stewardship interventions. Antimicrob. Steward. Healthc. Epidemiol. 2022 2 1 e8 10.1017/ash.2021.224 36310787
    [Google Scholar]
  22. Daniel E.M. Krupnick A.S. Heur Y.H. Blinzler J.A. Nims R.W. Stoner G.D. Extraction, stability, and quantitation of ellagic acid in various fruits and nuts. J. Food Compos. Anal. 1989 2 4 338 349 10.1016/0889‑1575(89)90005‑7
    [Google Scholar]
  23. Vella F.M. De Masi L. Calandrelli R. Morana A. Laratta B. Valorization of the agro-forestry wastes from Italian chestnut cultivars for the recovery of bioactive compounds. Eur. Food Res. Technol. 2019 245 12 2679 2686 10.1007/s00217‑019‑03379‑w
    [Google Scholar]
  24. Phan A.D.T. Zhang J. Seididamyeh M. Srivarathan S. Netzel M.E. Sivakumar D. Sultanbawa Y. Hydrolysable tannins, physicochemical properties, and antioxidant property of wild-harvested Terminalia ferdinandiana (exell) fruit at different maturity stages. Front. Nutr. 2022 9 961679 10.3389/fnut.2022.961679 35967775
    [Google Scholar]
  25. Fracassetti D. Costa C. Moulay L. Tomás-Barberán F.A. Ellagic acid derivatives, ellagitannins, proanthocyanidins and other phenolics, vitamin C and antioxidant capacity of two powder products from camu-camu fruit (Myrciaria dubia). Food Chem. 2013 139 1-4 578 588 10.1016/j.foodchem.2013.01.121 23561148
    [Google Scholar]
  26. Santos W.N.L. da Silva Sauthier M.C. dos Santos A.M.P. de Andrade Santana D. Almeida Azevedo R.S. da Cruz Caldas J. Simultaneous determination of 13 phenolic bioactive compounds in guava (Psidium guajava L.) by HPLC-PAD with evaluation using PCA and Neural Network Analysis (NNA). Microchem. J. 2017 133 583 592 10.1016/j.microc.2017.04.029
    [Google Scholar]
  27. García-Villalba R. Espín J.C. Aaby K. Alasalvar C. Heinonen M. Jacobs G. Voorspoels S. Koivumäki T. Kroon P.A. Pelvan E. Saha S. Tomás-Barberán F.A. Validated method for the characterization and quantification of extractable and nonextractable ellagitannins after acid hydrolysis in pomegranate fruits, juices, and extracts. J. Agric. Food Chem. 2015 63 29 6555 6566 10.1021/acs.jafc.5b02062 26158321
    [Google Scholar]
  28. Koponen J.M. Happonen A.M. Mattila P.H. Törrönen A.R. Contents of anthocyanins and ellagitannins in selected foods consumed in Finland. J. Agric. Food Chem. 2007 55 4 1612 1619 10.1021/jf062897a 17261015
    [Google Scholar]
  29. Akbari B. Baghaei-Yazdi N. Bahmaie M. Mahdavi Abhari F. The role of plant‐derived natural antioxidants in reduction of oxidative stress. Biofactors 2022 48 3 611 633 10.1002/biof.1831 35229925
    [Google Scholar]
  30. Gasmi J. Sanderson J.T. Growth inhibitory, antiandrogenic, and pro-apoptotic effects of punicic acid in LNCaP human prostate cancer cells. J. Agric. Food Chem. 2010 58 23 12149 12156 10.1021/jf103306k 21067181
    [Google Scholar]
  31. Mannino F. Imbesi C. Bitto A. Minutoli L. Squadrito F. D’Angelo T. Booz C. Pallio G. Irrera N. Anti-oxidant and anti-inflammatory effects of ellagic and punicic acid in an in vitro model of cardiac fibrosis. Biomed. Pharmacother. 2023 162 114666 10.1016/j.biopha.2023.114666 37030134
    [Google Scholar]
  32. Oyedepo T.A. Morakinyo A.E. Babarinde S.O. Immune boosting activity of nutraceuticals and functional foods. Immunomodulators and Human Health Singapore Springer Nature 2022 71 100 10.1007/978‑981‑16‑6379‑6_3
    [Google Scholar]
  33. Machado M. Costa E.M. Silva S. Rodriguez-Alcalá L.M. Gomes A.M. Pintado M. Pomegranate oil’s potential as an anti-obesity ingredient. Molecules 2022 27 15 4958 10.3390/molecules27154958 35956908
    [Google Scholar]
  34. Mohammadinejad A. Mohajeri T. Aleyaghoob G. Heidarian F. Kazemi Oskuee R. Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies. Biotechnol. Appl. Biochem. 2022 69 6 2323 2356 10.1002/bab.2288 34846078
    [Google Scholar]
  35. Ganai S.A. Sheikh F.A. Baba Z.A. Mir M.A. Mantoo M.A. Yatoo M.A. Anticancer activity of the plant flavonoid luteolin against preclinical models of various cancers and insights on different signalling mechanisms modulated. Phytother. Res. 2021 35 7 3509 3532 10.1002/ptr.7044 33580629
    [Google Scholar]
  36. Manso T. Lores M. de Miguel T. Antimicrobial activity of polyphenols and natural polyphenolic extracts on clinical isolates. Antibiotics 2021 11 1 46 10.3390/antibiotics11010046 35052923
    [Google Scholar]
  37. Tiwari D.S. Talreja S. Health benefits of cranberries: An in-depth overview. Health Sci. J. 2023 17 9 1 6
    [Google Scholar]
  38. Rojo-Gutiérrez E. Carrasco-Molinar O. Tirado-Gallegos J.M. Levario-Gómez A. Chávez-González M.L. Baeza-Jiménez R. Buenrostro-Figueroa J.J. Evaluation of green extraction processes, lipid composition and antioxidant activity of pomegranate seed oil. J. Food Meas. Charact. 2021 15 2 2098 2107 10.1007/s11694‑020‑00804‑7
    [Google Scholar]
  39. Bhandary B.S. Sharmila K.P. Kumari N.S. Bhat V.S. Assessment of anti-inflammatory activity of Punica granatum L. ethanol extracts and synthetic ellagic acid in Swiss albino mice. Am J Pharm Health Res. 2014 4 192 198
    [Google Scholar]
  40. Fourati M. Smaoui S. Hlima H.B. Elhadef K. Braïek O.B. Ennouri K. Mtibaa A.C. Mellouli L. Bioactive compounds and pharmacological potential of pomegranate (Punica granatum) seeds - A review. Plant Foods Hum. Nutr. 2020 75 4 477 486 10.1007/s11130‑020‑00863‑7 33040298
    [Google Scholar]
  41. Paul A. Radhakrishnan M. Pomegranate seed oil in food industry: Extraction, characterization, and applications. Trends Food Sci. Technol. 2020 105 273 283 10.1016/j.tifs.2020.09.014
    [Google Scholar]
  42. Jang Y.S. Mosolygó T. Inhibition of bacterial biofilm formation by phytotherapeutics with focus on overcoming antimicrobial resistance. Curr. Pharm. Des. 2020 26 24 2807 2816 10.2174/1381612826666200212121710 32048958
    [Google Scholar]
  43. Wang Y. The interplay of exercise and polyphenols in cancer treatment: A focus on oxidative stress and antioxidant mechanisms. Phytother. Res. 2024 38 7 3459 3488 10.1002/ptr.8215 38690720
    [Google Scholar]
  44. Promsong A. Chung W.O. Satthakarn S. Nittayananta W. Ellagic acid modulates the expression of oral innate immune mediators: Potential role in mucosal protection. J. Oral Pathol. Med. 2015 44 3 214 221 10.1111/jop.12223 25047680
    [Google Scholar]
  45. Panichayupakaranant P. Antibacterial activity of ellagic acid-rich pomegranate rind extracts. Planta Med. 2010 76 12 10.1055/s‑0030‑1264706
    [Google Scholar]
  46. Tirado-Gallegos J.M. Baeza-Jiménez R. Ascacio-Valdés J.A. Bustillos-Rodríguez J.C. Buenrostro-Figueroa J. Pomegranate seeds as a potential source of punicic acid: Extraction and nutraceutical benefits. Practical Applications of Physical Chemistry in Food Science and Technology. Apple Academic Press 2021 129 153 10.1201/9781003020004‑6
    [Google Scholar]
  47. Du M. Jin J. Wu G. Jin Q. Wang X. Metabolic, structure-activity characteristics of conjugated linolenic acids and their mediated health benefits. Crit. Rev. Food Sci. Nutr. 2024 64 23 8203 8217 10.1080/10408398.2023.2198006 37021469
    [Google Scholar]
  48. Muhsina AS Nandu TG Praseetha S Shiburaj S The antibacterial activity of ellagic acid from Punica granatum L. mediated through inhibition of bacterial divisome protein, FtsZ. J. Tradit. Folk Pract. 2021 9
    [Google Scholar]
  49. Adu-Frimpong M. Firempong C.K. Omari-Siaw E. Wang Q. Mukhtar Y.M. Deng W. Yu Q. Xu X. Yu J. Preparation, optimization, and pharmacokinetic study of nanoliposomes loaded with triacylglycerol‐bound punicic acid for increased antihepatotoxic activity. Drug Dev. Res. 2019 80 2 230 245 10.1002/ddr.21485 30414214
    [Google Scholar]
  50. Ceci C. Lacal P.M. Tentori L. De Martino M.G. Miano R. Graziani G. Experimental evidence of the antitumor, antimetastatic and antiangiogenic activity of ellagic acid. Nutrients 2018 10 11 1756 10.3390/nu10111756 30441769
    [Google Scholar]
  51. Viladomiu M. Hontecillas R. Lu P. Bassaganya-Riera J. Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents. Evid. Based Complement. Alternat. Med. 2013 2013 1 18 10.1155/2013/789764 23737845
    [Google Scholar]
  52. Doostkam A. Bassiri-Jahromi S. Iravani K. Punica granatum with multiple effects in chronic diseases. Int. J. Fruit Sci. 2020 20 3 471 494 10.1080/15538362.2019.1653809
    [Google Scholar]
  53. García-Niño W.R. Zazueta C. Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection. Pharmacol. Res. 2015 97 84 103 10.1016/j.phrs.2015.04.008 25941011
    [Google Scholar]
  54. Naraki K. Ghasemzadeh Rahbardar M. Ajiboye B.O. Hosseinzadeh H. The effect of ellagic acid on the metabolic syndrome: A review article. Heliyon 2023 9 11 e21844 e4 10.1016/j.heliyon.2023.e21844 38027887
    [Google Scholar]
  55. Čižmáriková M. Michalková R. Mirossay L. Mojžišová G. Zigová M. Bardelčíková A. Mojžiš J. Ellagic acid and cancer hallmarks: Insights from experimental evidence. Biomolecules 2023 13 11 1653 10.3390/biom13111653 38002335
    [Google Scholar]
  56. Murugan V. Mukherjee K. Maiti K. Mukherjee P.K. Enhanced oral bioavailability and antioxidant profile of ellagic acid by phospholipids. J. Agric. Food Chem. 2009 57 11 4559 4565 10.1021/jf8037105 19449806
    [Google Scholar]
  57. Ceci C. Tentori L. Atzori M. Lacal P. Bonanno E. Scimeca M. Cicconi R. Mattei M. De Martino M. Vespasiani G. Miano R. Graziani G. Ellagic acid inhibits bladder cancer invasiveness and in vivo tumor growth. Nutrients 2016 8 11 744 10.3390/nu8110744 27879653
    [Google Scholar]
  58. Mohammed Saleem Y. Selim M. MDM2 as a target for ellagic acid‑mediated suppression of prostate cancer cells in vitro. Oncol. Rep. 2020 44 3 1255 1265 10.3892/or.2020.7664 32705219
    [Google Scholar]
  59. Ansari L. Mahdinezhad M.R. Rakhshandeh H. Hosseini A. Noughabi S.B. Gholami N. Rajabian A. Acute and sub-acute toxicity assessment of the standardized extract of Sanguisorba minor in vivo. J. Complement. Integr. Med. 2022 19 4 987 997 10.1515/jcim‑2021‑0391 34881541
    [Google Scholar]
  60. Mosaddad S.A. Hussain A. Tebyaniyan H. Green alternatives as antimicrobial agents in mitigating periodontal diseases: A narrative review. Microorganisms 2023 11 5 1269 10.3390/microorganisms11051269 37317243
    [Google Scholar]
  61. Parisi V. Santoro V. Donadio G. Bellone M.L. Diretto G. Sandri C. Mensitieri F. De Tommasi N. Dal Piaz F. Braca A. Comparative chemical analysis of eight Punica granatum L. peel cultivars and their antioxidant and anti-inflammatory activities. Antioxidants 2022 11 11 2262 10.3390/antiox11112262 36421448
    [Google Scholar]
  62. Olvera-Sandoval C. Fabela-Illescas H.E. Fernández-Martínez E. Ortiz-Rodríguez M.A. Cariño-Cortés R. Ariza-Ortega J.A. Hernández-González J.C. Olivo D. Valadez-Vega C. Belefant-Miller H. Betanzos-Cabrera G. Potential mechanisms of the improvement of glucose homeostasis in type 2 diabetes by pomegranate juice. Antioxidants 2022 11 3 553 10.3390/antiox11030553 35326203
    [Google Scholar]
  63. Caruso A. Barbarossa A. Tassone A. Ceramella J. Carocci A. Catalano A. Basile G. Fazio A. Iacopetta D. Franchini C. Sinicropi M.S. Pomegranate: Nutraceutical with promising benefits on human health. Appl. Sci. (Basel) 2020 10 19 6915 10.3390/app10196915
    [Google Scholar]
  64. Mohamed S.S. Fayed A-H.M. Anti-obesity synergistic effect of pomegranate seed oil (PSO) and arabic gum (AG) in albino rats. Int. J. Vet. Sci. 2020 9 84 89
    [Google Scholar]
  65. Ferrari Cervi V. Parcianello Saccol C. Henrique Marcondes Sari M. Cristóvão Martins C. Saldanha da Rosa L. Dias Ilha B. Zovico Soares F. Luchese C. Antunes Wilhelm E. Cruz L. Pullulan film incorporated with nanocapsules improves pomegranate seed oil anti-inflammatory and antioxidant effects in the treatment of atopic dermatitis in mice. Int. J. Pharm. 2021 609 121144 10.1016/j.ijpharm.2021.121144 34600055
    [Google Scholar]
  66. Kaye K.S. Gupta V. Mulgirigama A. Joshi A.V. Scangarella-Oman N.E. Yu K. Ye G. Mitrani-Gold F.S. Antimicrobial resistance trends in urine Escherichia coli isolates from adult and adolescent females in the United States from 2011 to 2019: Rising ESBL strains and impact on patient management. Clin. Infect. Dis. 2021 73 11 1992 1999 10.1093/cid/ciab560 34143881
    [Google Scholar]
  67. Evtyugin D.D. Magina S. Evtuguin D.V. Recent advances in the production and applications of ellagic acid and its derivatives. A review. Molecules 2020 25 12 2745 10.3390/molecules25122745 32545813
    [Google Scholar]
  68. Meerts I.A.T.M. Verspeek-Rip C.M. Buskens C.A.F. Keizer H.G. Bassaganya-Riera J. Jouni Z.E. van Huygevoort A.H.B.M. van Otterdijk F.M. van de Waart E.J. Toxicological evaluation of pomegranate seed oil. Food Chem. Toxicol. 2009 47 6 1085 1092 10.1016/j.fct.2009.01.031 19425183
    [Google Scholar]
  69. Pereira de Melo I.L. de Oliveira e Silva A.M. Yoshime L.T. Gasparotto Sattler J.A. Teixeira de Carvalho E.B. Mancini-Filho J. Punicic acid was metabolised and incorporated in the form of conjugated linoleic acid in different rat tissues. Int. J. Food Sci. Nutr. 2019 70 4 421 431 10.1080/09637486.2018.1519528 30326753
    [Google Scholar]
  70. Zacchè M.M. Giarenis I. Therapies in early development for the treatment of urinary tract inflammation. Expert Opin. Investig. Drugs 2016 25 5 531 540 10.1517/13543784.2016.1161024 26934616
    [Google Scholar]
  71. Saha S.S. Dasgupta P. Sengupta Bandyopadhyay S. Ghosh M. Synergistic effect of conjugated linolenic acid isomers against induced oxidative stress, inflammation and erythrocyte membrane disintegrity in rat model. Biochim. Biophys. Acta 2012 1820 12 1951 1970 10.1016/j.bbagen.2012.08.021 22967758
    [Google Scholar]
  72. Bialonska D. Kasimsetty S.G. Schrader K.K. Ferreira D. The effect of pomegranate (Punica granatum L.) byproducts and ellagitannins on the growth of human gut bacteria. J. Agric. Food Chem. 2009 57 18 8344 8349 10.1021/jf901931b 19705832
    [Google Scholar]
  73. Gabizon R. Binyamin O. Larush L. Frid K. Keller G. Friedman-Levi Y. Ovadia H. Abramsky O. Magdassi S. Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant. Int. J. Nanomedicine 2015 10 7165 7174 10.2147/IJN.S92704 26648720
    [Google Scholar]
  74. Loubet P. Ranfaing J. Dinh A. Dunyach-Remy C. Bernard L. Bruyère F. Lavigne J.P. Sotto A. Alternative therapeutic options to antibiotics for the treatment of urinary tract infections. Front. Microbiol. 2020 11 1509 10.3389/fmicb.2020.01509 32719668
    [Google Scholar]
  75. Ledda A. Hu S. Cesarone M.R. Belcaro G. Dugall M. Feragalli B. Cotellese R. Hosoi M. Ippolito E. Corsi M. Luzzi R. Pycnogenol® supplementation prevents recurrent urinary tract infections/inflammation and interstitial cystitis. Evid. Based Complement. Alternat. Med. 2021 2021 1 8 10.1155/2021/9976299 34257695
    [Google Scholar]
  76. Noce A. Di Daniele F. Campo M. Di Lauro M. Pietroboni Zaitseva A. Di Daniele N. Marrone G. Romani A. Effect of hydrolysable tannins and anthocyanins on recurrent urinary tract infections in nephropathic patients: Preliminary data. Nutrients 2021 13 2 591 10.3390/nu13020591 33670236
    [Google Scholar]
  77. Wang L. Li W. Lin M. Garcia M. Mulholland D. Lilly M. Martins-Green M. Luteolin, ellagic acid and punicic acid are natural products that inhibit prostate cancer metastasis. Carcinogenesis 2014 35 10 2321 2330 10.1093/carcin/bgu145 25023990
    [Google Scholar]
  78. Albrecht M. Jiang W. Kumi-Diaka J. Lansky E.P. Gommersall L.M. Patel A. Mansel R.E. Neeman I. Geldof A.A. Campbell M.J. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J. Med. Food 2004 7 3 274 283 10.1089/jmf.2004.7.274 15383219
    [Google Scholar]
  79. Pitchakarn P. Chewonarin T. Ogawa K. Suzuki S. Asamoto M. Takahashi S. Shirai T. Limtrakul P. Ellagic acid inhibits migration and invasion by prostate cancer cell lines. Asian Pac. J. Cancer Prev. 2013 14 5 2859 2863 10.7314/APJCP.2013.14.5.2859 23803044
    [Google Scholar]
  80. Mighani S. Samimi R. Nooshabadi M.R. Farzam S.A. Haghighian H.K. Javadi M. A randomized double-blind clinical trial investigating the effects of ellagic acid on glycemic status, liver enzymes, and oxidative stress in patients with non-alcoholic fatty liver disease. BMC Complement. Med. Ther. 2025 25 1 33 10.1186/s12906‑025‑04759‑4 39885430
    [Google Scholar]
  81. Wong T.L. Strandberg K.R. Croley C.R. Fraser S.E. Nagulapalli Venkata K.C. Fimognari C. Sethi G. Bishayee A. Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention. Semin. Cancer Biol. 2021 73 265 293 10.1016/j.semcancer.2021.01.006 33503488
    [Google Scholar]
  82. Kroeger N. 1,2 belldegrun a. s.,1 and pantuck a. j.1. pomegranate extracts in the management of men’s urologic health: Scientific rationale and preclinical and clinical data. Evid. Based Complement. Alternat. Med. 2013 2013 1 9 10.1155/2013/870454
    [Google Scholar]
  83. Jafari Karegar S. Aryaeian N. Hajiluian G. Suzuki K. Shidfar F. Salehi M. Ashtiani B.H. Farhangnia P. Delbandi A.A. Ellagic acid effects on disease severity, levels of cytokines and T-bet, RORγt, and GATA3 genes expression in multiple sclerosis patients: A multicentral-triple blind randomized clinical trial. Front. Nutr. 2023 10 1238846 10.3389/fnut.2023.1238846
    [Google Scholar]
  84. Freedland S. Carducci M. Kroeger N. Partin A. Rao J. Jin Y. Kerkoutian S. Wu H. Li Y.F. Creel P. Mundy K. Gurganus R. Fedor H. King S. Heber D. Zhang Y. Pantuck A. 174 A phase II randomized controlled trial of POMX vs. placebo prior to radical prostatectomy. J. Urol. 2012 187 4S 73 10.1016/j.juro.2012.02.225
    [Google Scholar]
  85. Kazemi M. Lalooha F. Nooshabadi M.R. Dashti F. Kavianpour M. Haghighian H.K. Randomized double blind clinical trial evaluating the Ellagic acid effects on insulin resistance, oxidative stress and sex hormones levels in women with polycystic ovarian syndrome. J. Ovarian Res. 2021 14 1 100 10.1186/s13048‑021‑00849‑2 34330312
    [Google Scholar]
  86. Abubakar A. Haque M. Preparation of medicinal plants: Basic extraction and fractionation procedures for experimental purposes. J. Pharm. Bioallied Sci. 2020 12 1 1 10 10.4103/jpbs.JPBS_175_19 32801594
    [Google Scholar]
  87. Pantuck A.J. Leppert J.T. Zomorodian N. Aronson W. Hong J. Barnard R.J. Seeram N. Liker H. Wang H. Elashoff R. Heber D. Aviram M. Ignarro L. Belldegrun A. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin. Cancer Res. 2006 12 13 4018 4026 10.1158/1078‑0432.CCR‑05‑2290 16818701
    [Google Scholar]
  88. Uwineza P.A. Waśkiewicz A. Recent advances in supercritical fluid extraction of natural bioactive compounds from natural plant materials. Molecules 2020 25 17 3847 10.3390/molecules25173847 32847101
    [Google Scholar]
  89. Hidad S. van der Putten B. van Houdt R. Schneeberger C. Kuil S.D. Recurrent E. coli urinary tract infections in nursing homes: insight in sequence types and antibiotic resistance patterns. Antibiotics 2022 11 11 1638 10.3390/antibiotics11111638 36421283
    [Google Scholar]
  90. Fayers PM Machin D Quality of Life: The Assessment, Analysis and Interpretation of Patient-Reported Outcomes England 2013
    [Google Scholar]
  91. Yuan G.F. Yuan J.Q. Li D. Punicic acid from Trichosanthes kirilowii seed oil is rapidly metabolized to conjugated linoleic acid in rats. J. Med. Food 2009 12 2 416 422 10.1089/jmf.2007.0541 19459746
    [Google Scholar]
  92. Golmei P. Kasna S. Roy K.P. Kumar S. A review on pharmacological advancement of ellagic acid. J. Pharmacol. Pharmacother. 2024 15 2 93 104 10.1177/0976500X241240634
    [Google Scholar]
  93. Cota D. Patil D. Antibacterial potential of ellagic acid and gallic acid against IBD bacterial isolates and cytotoxicity against colorectal cancer. Nat. Prod. Res. 2023 37 12 1998 2002 10.1080/14786419.2022.2111560 35968644
    [Google Scholar]
  94. Duan D. Xie H. Jiang J. Yang P. Guo Z. Guo X. Chen X. Yao Q. Permeability-Enhancing and protective effect on small intestine of punicic acid in different forms and their nanoemulsions with low toxicity. Int. J. Nanomedicine 2025 20 1579 1596 10.2147/IJN.S486709 39931527
    [Google Scholar]
  95. Lin C.C. Huang Y.C. Lee W.C. Chuang Y.C. New frontiers or the treatment of interstitial cystitis/bladder pain syndrome - Focused on stem cells, platelet-rich plasma, and low-energy shock wave. Int. Neurourol. J. 2020 24 3 211 221 10.5213/inj.2040104.052 33017892
    [Google Scholar]
  96. Cox S. Vleeming M. Giorgi W. Dinant G.J. Cals J. de Bont E. Patients’ experiences, expectations, motivations, and perspectives around urinary tract infection care in general practice: A qualitative interview study. Antibiotics 2023 12 2 241 10.3390/antibiotics12020241 36830152
    [Google Scholar]
  97. Milano A. Sulejmani A. Intra J. Sala M.R. Leoni V. Carcione D. Antimicrobial resistance trends of Escherichia coli isolates from outpatient and inpatient urinary infections over a 20-year period. Microb. Drug Resist. 2022 28 1 63 72 10.1089/mdr.2021.0010 34520265
    [Google Scholar]
  98. Ramjane H. Bahorun T. Ramasawmy B. Ramful-Baboolall D. Boodia N. Aruoma O.I. Neergheen V.S. Exploration of the potential of terrestrial and marine biodiversity for the development of local nutraceutical products: A case for Mauritius. Am. J. Biopharma. Pharma. Sci. 2021 1 3 10.25259/AJBPS_3_2021
    [Google Scholar]
  99. Ansari M.T. Srivastava D. Ali O.A. Hau T.W. Sami F. Hasnain M.S. Chapter 17 - Advances in semisolid dosage form. Dosage Forms, Formulation Developments and Regulations Academic Press 2024 519 542 10.1016/B978‑0‑323‑91817‑6.00018‑8
    [Google Scholar]
  100. Benedetti G. Zabini F. Tagliavento L. Meneguzzo F. Calderone V. Testai L. An overview of the health benefits, extraction methods and improving the properties of pomegranate. Antioxidants 2023 12 7 1351 10.3390/antiox12071351 37507891
    [Google Scholar]
  101. Herzyk F. Piłakowska-Pietras D. Korzeniowska M. Supercritical extraction techniques for obtaining biologically active substances from a variety of plant byproducts. Foods 2024 13 11 1713 10.3390/foods13111713 38890941
    [Google Scholar]
  102. Khoddami A. Man Y.B.C. Roberts T.H. Physico‐chemical properties and fatty acid profile of seed oils from pomegranate (Punica granatum L.) extracted by cold pressing. Eur. J. Lipid Sci. Technol. 2014 116 5 553 562 10.1002/ejlt.201300416
    [Google Scholar]
  103. Ellagic acid - Uses, side effects, and more. Available from: https://www.webmd.com/vitamins/ai/ingredientmono-1074/ellagic-acid
  104. Mendes P.M. Gomes Fontoura G.M. Rodrigues L.S. Souza A.S. Viana J.P.M. Fernandes Pereira A.L. Dutra R.P. Nogueira Ferreira A.G. Neto M.S. Reis A.S. Berretta A.A. Monteiro-Neto V. Maciel M.C.G. Therapeutic potential of Punica granatum and isolated compounds: Evidence-based advances to treat bacterial infections. Int. J. Microbiol. 2023 2023 1 15 10.1155/2023/4026440 38144901
    [Google Scholar]
  105. Baradaran Rahimi V. Ghadiri M. Ramezani M. Askari V.R. Antiinflammatory and anti‐cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies. Phytother. Res. 2020 34 4 685 720 10.1002/ptr.6565 31908068
    [Google Scholar]
  106. Cortez-Trejo M.C. Wall-Medrano A. Gaytán-Martínez M. Mendoza S. Microencapsulation of pomegranate seed oil using a succinylated taro starch: Characterization and bioaccessibility study. Food Biosci. 2021 41 100929 10.1016/j.fbio.2021.100929
    [Google Scholar]
  107. Preeti Sambhakar S. Malik R. Bhatia S. Al Harrasi A. Rani C. Saharan R. Kumar S. Geeta Sehrawat R. Nanoemulsion: An emerging novel technology for improving the bioavailability of drugs. Scientifica 2023 2023 1 25 10.1155/2023/6640103 37928749
    [Google Scholar]
  108. Binyamin O. Nitzan K. Frid K. Ungar Y. Rosenmann H. Gabizon R. Brain targeting of 9c,11t-Conjugated Linoleic Acid, a natural calpain inhibitor, preserves memory and reduces Aβ and P25 accumulation in 5XFAD mice. Sci. Rep. 2019 9 1 18437 10.1038/s41598‑019‑54971‑9 31804596
    [Google Scholar]
  109. Yu Z.J. Yan H.L. Xu F.H. Chao H.C. Deng L.H. Xu X.D. Huang J.B. Zeng T. Efficacy and side effects of drugs commonly used for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Front. Pharmacol. 2020 11 658 10.3389/fphar.2020.00658 32457631
    [Google Scholar]
  110. Wang S. Cheng Y. Wang J. Ding M. Fan Z. Antioxidant activity, formulation, optimization and characterization of an oil-in-water nanoemulsion loaded with lingonberry (Vaccinium vitis-idaea L.) leaves polyphenol extract. Foods 2023 12 23 4256 10.3390/foods12234256 38231701
    [Google Scholar]
  111. Tyers M. Wright G.D. Drug combinations: A strategy to extend the life of antibiotics in the 21st century. Nat. Rev. Microbiol. 2019 17 3 141 155 10.1038/s41579‑018‑0141‑x 30683887
    [Google Scholar]
  112. Sullivan G.J. Delgado N.N. Maharjan R. Cain A.K. How antibiotics work together: Molecular mechanisms behind combination therapy. Curr. Opin. Microbiol. 2020 57 31 40 10.1016/j.mib.2020.05.012 32619833
    [Google Scholar]
  113. Von Vietinghoff S. Shevchuk O. Dobrindt U. Engel D.R. Jorch S.K. Kurts C. Miethke T. Wagenlehner F. The global burden of antimicrobial resistance – Urinary tract infections. Nephrol. Dial. Transplant. 2024 39 4 581 588 10.1093/ndt/gfad233 37891013
    [Google Scholar]
  114. Santos F.H. Panda S.K. Ferreira D.C.M. Dey G. Molina G. Pelissari F.M. Targeting infections and inflammation through micro and nano-nutraceuticals. Food Biosci. 2022 49 101891 10.1016/j.fbio.2022.101891
    [Google Scholar]
  115. Wu X. Study of the extraction process and nutritional benefits of bioactive compounds in pomegranate peel. Doctor of Philosophy, University of California 2021
    [Google Scholar]
  116. Guerra-Vázquez C.M. Martínez-Ávila M. Guajardo-Flores D. Antunes-Ricardo M. Punicic acid and its role in the prevention of neurological disorders: A review. Foods 2022 11 3 252 10.3390/foods11030252 35159404
    [Google Scholar]
  117. Ku J.H. Bruxvoort K.J. Salas S.B. Varley C.D. Casey J.A. Raphael E. Robinson S.C. Nachman K.E. Lewin B.J. Contreras R. Wei R.X. Pomichowski M.E. Takhar H.S. Tartof S.Y. Multidrug resistance of Escherichia coli from outpatient uncomplicated urinary tract infections in a large United States integrated healthcare organization. Open Forum Infect. Dis. 2023 10 7 ofad287 10.1093/ofid/ofad287 37426945
    [Google Scholar]
  118. Wang L. Martins-Green M. Pomegranate and its components as alternative treatment for prostate cancer. Int. J. Mol. Sci. 2014 15 9 14949 14966 10.3390/ijms150914949 25158234
    [Google Scholar]
  119. Agrawal O.D. Kulkarni Y.A. Mini-review of analytical methods used in quantification of ellagic acid. Rev. Anal. Chem. 2020 39 1 31 44 10.1515/revac‑2020‑0113
    [Google Scholar]
  120. Jain V. Shaikh S. Development and validation of novel RP-HPLC method for the simultaneous estimation of ellagic acid and quercetin in an ayurvedic formulation. Int. J. Appl. Pharm. 2018 10 4 111 10.22159/ijap.2018v10i4.27011
    [Google Scholar]
  121. Murray C.J.L. Ikuta K.S. Sharara F. Swetschinski L. Robles Aguilar G. Gray A. Han C. Bisignano C. Rao P. Wool E. Johnson S.C. Browne A.J. Chipeta M.G. Fell F. Hackett S. Haines-Woodhouse G. Kashef Hamadani B.H. Kumaran E.A.P. McManigal B. Achalapong S. Agarwal R. Akech S. Albertson S. Amuasi J. Andrews J. Aravkin A. Ashley E. Babin F-X. Bailey F. Baker S. Basnyat B. Bekker A. Bender R. Berkley J.A. Bethou A. Bielicki J. Boonkasidecha S. Bukosia J. Carvalheiro C. Castañeda-Orjuela C. Chansamouth V. Chaurasia S. Chiurchiù S. Chowdhury F. Clotaire Donatien R. Cook A.J. Cooper B. Cressey T.R. Criollo-Mora E. Cunningham M. Darboe S. Day N.P.J. De Luca M. Dokova K. Dramowski A. Dunachie S.J. Duong Bich T. Eckmanns T. Eibach D. Emami A. Feasey N. Fisher-Pearson N. Forrest K. Garcia C. Garrett D. Gastmeier P. Giref A.Z. Greer R.C. Gupta V. Haller S. Haselbeck A. Hay S.I. Holm M. Hopkins S. Hsia Y. Iregbu K.C. Jacobs J. Jarovsky D. Javanmardi F. Jenney A.W.J. Khorana M. Khusuwan S. Kissoon N. Kobeissi E. Kostyanev T. Krapp F. Krumkamp R. Kumar A. Kyu H.H. Lim C. Lim K. Limmathurotsakul D. Loftus M.J. Lunn M. Ma J. Manoharan A. Marks F. May J. Mayxay M. Mturi N. Munera-Huertas T. Musicha P. Musila L.A. Mussi-Pinhata M.M. Naidu R.N. Nakamura T. Nanavati R. Nangia S. Newton P. Ngoun C. Novotney A. Nwakanma D. Obiero C.W. Ochoa T.J. Olivas-Martinez A. Olliaro P. Ooko E. Ortiz-Brizuela E. Ounchanum P. Pak G.D. Paredes J.L. Peleg A.Y. Perrone C. Phe T. Phommasone K. Plakkal N. Ponce-de-Leon A. Raad M. Ramdin T. Rattanavong S. Riddell A. Roberts T. Robotham J.V. Roca A. Rosenthal V.D. Rudd K.E. Russell N. Sader H.S. Saengchan W. Schnall J. Scott J.A.G. Seekaew S. Sharland M. Shivamallappa M. Sifuentes-Osornio J. Simpson A.J. Steenkeste N. Stewardson A.J. Stoeva T. Tasak N. Thaiprakong A. Thwaites G. Tigoi C. Turner C. Turner P. van Doorn H.R. Velaphi S. Vongpradith A. Vongsouvath M. Vu H. Walsh T. Walson J.L. Waner S. Wangrangsimakul T. Wannapinij P. Wozniak T. Young Sharma T.E.M.W. Yu K.C. Zheng P. Sartorius B. Lopez A.D. Stergachis A. Moore C. Dolecek C. Naghavi M. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022 399 10325 629 655 10.1016/S0140‑6736(21)02724‑0 35065702
    [Google Scholar]
  122. Heidarian E. Eskandari E. Amini S. Saffari-Chaleshtori J. Evaluating the effects of ellagic acid on pSTAT3, pAKT, and pERK1/2 signaling pathways in prostate cancer PC3 cells. J. Cancer Res. Ther. 2016 12 4 1266 1271 10.4103/0973‑1482.165873 28169238
    [Google Scholar]
/content/journals/cmm/10.2174/0115665240378450250410073416
Loading
Innovative Therapeutic Potential of Herbal Extracts Containing Punicic and Ellagic Acid: Addressing Lower Urinary Tract Disorders
Bentham Science Publishers ; https://doi.org/10.2174/0115665240378450250410073416
/content/journals/cmm/10.2174/0115665240378450250410073416
/content/journals/cmm/10.2174/0115665240378450250410073416
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: lower urinary tract disorders ; antioxidant ; herbal extracts ; ellagic acid ; Punicic acid ; anti-inflammatory

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test