Skip to content
2000
Volume 4, Issue 1
  • ISSN: 2210-299X
  • E-ISSN: 2210-3007

Abstract

Urolithiasis is a disorder affecting approximately 12% of the world's population, and has a recurrence rate of 47-60% in women and 70-80% in men. The standard therapeutic drugs used for the prevention and treatment of urolithiasis include allopurinol, citrate, cystone, and thiazide diuretics; yet, because of the recurrence of kidney stones and other adverse effects, these drugs are not always effective. All these consequences of surgical treatment result in stone recurrence, hypertension, and chronic renal injury. Reactive oxygen species (ROS) and oxidative stress (OS) have been identified in numerous studies as key pathogenic contributors to the development of stones. Dietary polyphenols are a broad class of naturally occurring antioxidant chemicals that are found in many plant-based foods and drinks. A broad class of naturally occurring antioxidant molecules found in many plant-based foods and drinks is called dietary polyphenols. In recent decades, their many health advantages have drawn increasing scientific interest. The usefulness of dietary polyphenols in preventing the formation of stones has been documented. Based on recent studies, plant flavonoids can potentially inhibit the formation of CaOx stones both and . This is consistent with their diuretic, antioxidant, anti-inflammatory, antibacterial, and other preventive activities. The plant extracts that contain flavonoids or flavonoid-containing compounds and possess anti-urolithiasis activity have been assessed, as well as their probable mechanisms of action. Furthermore, we have provided opportunities and obstacles in transforming plant flavonoids into medications that prevent stones, as well as some issues that should be considered in future research. Urolithiasis can be effectively treated using various medicinal herbs with diuretic, antispasmodic, and antioxidant properties. These plants also limit the nucleation, aggregation, and crystallization of crystals. Natural polyphenols show strong binding affinity (Ka = 104–106 M−1) toward proteins and DNA through hydrogen bonding, van der Waals, and hydrophobic interactions, with negative ΔG indicating spontaneous interaction.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cis/10.2174/012210299X401377251115094018
2025-11-24
2026-02-23
Loading full text...

Full text loading...

/deliver/fulltext/cis/4/1/CIS-4-E2210299X401377.html?itemId=/content/journals/cis/10.2174/012210299X401377251115094018&mimeType=html&fmt=ahah

References

  1. AllamE.A.H. Urolithiasis unveiled: Pathophysiology, stone dynamics, types, and inhibitory mechanisms: A review.Afr. J. Urol.20243013410.1186/s12301‑024‑00436‑z
    [Google Scholar]
  2. PandeyK.B. RizviS.I. Plant polyphenols as dietary antioxidants in human health and disease.Oxid. Med. Cell. Longev.20092527027810.4161/oxim.2.5.949820716914
    [Google Scholar]
  3. RatkalkarV.N. KleinmanJ.G. Mechanisms of stone formation.Clin. Rev. Bone Miner. Metab.201193-418719710.1007/s12018‑011‑9104‑822229020
    [Google Scholar]
  4. ZhuoD. LiM. ChengL. ZhangJ. HuangH. YaoY. A study of diet and lifestyle and the risk of urolithiasis in 1,519 patients in Southern China.Med. Sci. Monit.2019254217422410.12659/MSM.91670331170122
    [Google Scholar]
  5. LópezM. HoppeB. History, epidemiology and regional diversities of urolithiasis.Pediatr. Nephrol.2010251495910.1007/s00467‑008‑0960‑521476230
    [Google Scholar]
  6. LiS. ZhouD. ZhuZ. TanX. TangW. GongJ. Boosting inhibition performance of natural polyphenols for the prevention of calcium oxalate kidney stones through synergistic cooperativity.Commun. Mater.2023416710.1038/s43246‑023‑00393‑0
    [Google Scholar]
  7. RathodN.B. ElabedN. PuniaS. OzogulF. KimS.K. RochaJ.M. Recent developments in polyphenol applications on human health: A review with current knowledge.Plants2023126121710.3390/plants1206121736986905
    [Google Scholar]
  8. de AraújoF.F. de Paulo FariasD. Neri-NumaI.A. PastoreG.M. Polyphenols and their applications: An approach in food chemistry and innovation potential.Food Chem.202133812753510.1016/j.foodchem.2020.12753532798817
    [Google Scholar]
  9. GulzarA. JavedA. LiaquatA. JavedD. ZahidM. MumtazH. Lifestyle and dietary habits change before and during quarantine and subsequent weight gain.J. Community Hosp. Intern. Med. Perspect.2023133283410.55729/2000‑9666.117637877054
    [Google Scholar]
  10. WaddenT.A. TronieriJ.S. ButrynM.L. Lifestyle modification approaches for the treatment of obesity in adults.Am. Psychol.202075223525110.1037/amp000051732052997
    [Google Scholar]
  11. HongS.Y. QinB.L. The protective role of dietary polyphenols in urolithiasis: Insights into antioxidant effects and mechanisms of action.Nutrients20231517375310.3390/nu1517375337686790
    [Google Scholar]
  12. ZhaoY. JiangQ. Roles of the polyphenol–gut microbiota interaction in alleviating colitis and preventing colitis-associated colorectal cancer.Adv. Nutr.202112254656510.1093/advances/nmaa10432905583
    [Google Scholar]
  13. HeferM. HuskicI.M. PetrovicA. Raguz-LucicN. KizivatT. GjoniD. HorvaticE. UdiljakZ. SmolicR. VcevA. SmolicM. A mechanistic insight into Beneficial effects of polyphenols in the prevention and treatment of Nephrolithiasis: Evidence from recent in vitro studies.Crystals2023137107010.3390/cryst13071070
    [Google Scholar]
  14. ZhangS. XuM. ZhangW. LiuC. ChenS. Natural polyphenols in metabolic syndrome: protective mechanisms and clinical applications.Int. J. Mol. Sci.20212211611010.3390/ijms2211611034204038
    [Google Scholar]
  15. PeerapenP. ThongboonkerdV. Kidney stone prevention.Adv. Nutr.202314355556910.1016/j.advnut.2023.03.00236906146
    [Google Scholar]
  16. Pacheco-HernándezB. Ayora-TalaveraT. Cano-SosaJ. NoriegaL.G. Pacheco-LópezN.A. Vargas-MoralesJ.M. Medina-VeraI. Guevara-CruzM. Chim-AkéR. Gutiérrez-SolisA.L. LugoR. Avila-NavaA. Antioxidant and Anti-Inflammatory Effects of Traditional Medicinal Plants for Urolithiasis: A Scoping Review.Plants20251413203210.3390/plants1413203240648041
    [Google Scholar]
  17. RamelloA. VitaleC. MarangellaM. Epidemiology of nephrolithiasis.J. Nephrol.200013Suppl. 3S45S5011132032
    [Google Scholar]
  18. GirijaE. Mineralogical composition of urinary calculi from southern India.J. Sci. Ind. Res. (India)200766632639
    [Google Scholar]
  19. ArumuhamV. BycroftJ. The management of urolithiasis.Surgery201634735236010.1016/j.mpsur.2016.04.007
    [Google Scholar]
  20. BartgesJ. Urolithiasis.Textbook of Small Animal Emergency MedicineHoboken, New JerseyJohn Wiley & Sons2018620626
    [Google Scholar]
  21. MoosaviB. FasihN. VirmaniV. KielarA. Beyond ureterolithiasis: Gamut of abnormalities affecting the ureter.Clin. Imaging201640467869010.1016/j.clinimag.2016.01.00327317212
    [Google Scholar]
  22. PanzarinoV. Urolithiasis in Children.Adv. Pediatr.20206710511210.1016/j.yapd.2020.03.00432591054
    [Google Scholar]
  23. BasavarajD.R. BiyaniC.S. BrowningA.J. CartledgeJ.J. The role of urinary kidney stone inhibitors and promoters in the pathogenesis of calcium containing renal stones.EAU-EBU Update Ser.20075312613610.1016/j.eeus.2007.03.002
    [Google Scholar]
  24. YingX. ChenY. HaoZ. LiuH. The significance of reactive oxygen species in the formation of calcium oxalate stones and the protective effects of antioxidants on the kidneys.Front. Immunol.202516154007510.3389/fimmu.2025.154007540469275
    [Google Scholar]
  25. AbrahamsH.M. MengM.V. StollerM.L. Urinary Stone Inhibitors: Citrate and Magnesium.Springer200710.1007/978‑1‑59259‑972‑1_9
    [Google Scholar]
  26. ZhaiW. ZhengJ. YaoX. PengB. LiuM. HuangJ. WangG. XuY. Catechin prevents the calcium oxalate monohydrate induced renal calcium crystallization in NRK-52E cells and the ethylene glycol induced renal stone formation in rat.BMC Complement. Altern. Med.201313122810.1186/1472‑6882‑13‑22824044655
    [Google Scholar]
  27. González-SarríasA. García-VillalbaR. Núñez-SánchezM.Á. Tomé-CarneiroJ. ZafrillaP. MuleroJ. Tomás-BarberánF.A. EspínJ.C. Identifying the limits for ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts.J. Funct. Foods20151922523510.1016/j.jff.2015.09.019
    [Google Scholar]
  28. Cechinel-ZanchettC.C. Bolda MarianoL.N. SchlickmannF. Cechinel-FilhoV. de SouzaP. In vitro effects of two bioactive compounds, gallic acid and methyl gallate, on urolithiasis.Actas Urol. Esp. (Engl. Ed.)202145960460810.1016/j.acuroe.2020.09.01034690102
    [Google Scholar]
  29. ShenS. WeiJ. KangW. WangT. Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol.J. Transl. Med.202321149110.1186/s12967‑023‑04356‑437480086
    [Google Scholar]
  30. PawarA. DeshmukhC. BhanudasB. GhodasaraJ. Inhibitory effect of rutin and curcumin on experimentally-induced calcium oxalate urolithiasis in rats.Pharmacognosy Res.20102638839210.4103/0974‑8490.7546221713144
    [Google Scholar]
  31. YuanP. SunX. LiuX. HuttererG. PummerK. HagerB. YeZ. ChenZ. Kaempferol alleviates calcium oxalate crystal-induced renal injury and crystal deposition via regulation of the AR/NOX2 signaling pathway.Phytomedicine20218615355510.1016/j.phymed.2021.15355533852977
    [Google Scholar]
  32. Saima AnjumI. MobasharA. JahanS. NajmS. Spasmolytic and uroprotective effects of apigenin by downregulation of TGF-β and iNOS pathways and upregulation of antioxidant mechanisms: in vitro and in silico analysis.Pharmaceutics202316681110.3390/ph16060811
    [Google Scholar]
  33. AzimiA. EidiA. MortazaviP. RohaniA.H. Protective effect of apigenin on ethylene glycol-induced urolithiasis via attenuating oxidative stress and inflammatory parameters in adult male Wistar rats.Life Sci.202127911964110.1016/j.lfs.2021.11964134043992
    [Google Scholar]
  34. RenQ. TaoS. GuoF. WangB. YangL. MaL. FuP. Natural flavonol fisetin attenuated hyperuricemic nephropathy via inhibiting IL-6/JAK2/STAT3 and TGF-β/SMAD3 signaling.Phytomedicine20218715355210.1016/j.phymed.2021.15355233994251
    [Google Scholar]
  35. YuL. GanX. LiuX. AnR. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.Ren. Fail.201739144045110.1080/0886022X.2017.130596828335665
    [Google Scholar]
  36. KhanS.R. ByerK.J. ThamilselvanS. HackettR.L. McCormackW.T. BensonN.A. VaughnK.L. ErdosG.W. Crystal-cell interaction and apoptosis in oxalate-associated injury of renal epithelial cells.J. Am. Soc. Nephrol.199910S457S46310541283
    [Google Scholar]
  37. MingS. TianJ. MaK. PeiC. LiL. WangZ. FangZ. LiuM. DongH. LiW. ZengJ. PengY. GaoX. Oxalate-induced apoptosis through ERS-ROS–NF-κB signalling pathway in renal tubular epithelial cell.Mol. Med.20222818810.1186/s10020‑022‑00494‑535922749
    [Google Scholar]
  38. DeviA.T. NagarajR. PrasadA. LakkappaD.B. ZameerF. NagalingaswamyN.P.M. Nephrolithiasis: Insights into biomimics, pathogenesis, and pharmacology.Clin. Complement. Med. Pharmacol.20233210007710.1016/j.ccmp.2022.100077
    [Google Scholar]
  39. TamborinoF. CicchettiR. MascittiM. LitterioG. OrsiniA. FerrettiS. BasconiM. De PalmaA. FerroM. MarchioniM. SchipsL. Pathophysiology and main molecular mechanisms of urinary stone formation and recurrence.Int. J. Mol. Sci.2024255307510.3390/ijms2505307538474319
    [Google Scholar]
  40. NirumandM. HajialyaniM. RahimiR. FarzaeiM. ZingueS. NabaviS. BishayeeA. Dietary plants for the prevention and management of kidney stones: Preclinical and clinical evidence and molecular mechanisms.Int. J. Mol. Sci.201819376510.3390/ijms1903076529518971
    [Google Scholar]
  41. HanX. ShenT. LouH. Dietary polyphenols and their biological significance.Int. J. Mol. Sci.2007895098810.3390/i8090950
    [Google Scholar]
  42. AliA. DeokuleS.S. Comparison of phenolic compounds of some edible plants of Iran and India.Pak. J. Nutr.200828
    [Google Scholar]
  43. ChaiyaritS. PhuangkhamS. ThongboonkerdV. Quercetin inhibits calcium oxalate crystallization and growth but promotes crystal aggregation and invasion.Curr. Res. Food Sci.2024810065010.1016/j.crfs.2023.10065038145155
    [Google Scholar]
  44. JeongB.C. KimB.S. KimJ.I. KimH.H. Effects of green tea on urinary stone formation: An in vivo and in vitro study.J. Endourol.200620535636110.1089/end.2006.20.35616724910
    [Google Scholar]
  45. PeerapenP. PutpeerawitP. BoonmarkW. ThongboonkerdV. Resveratrol inhibits calcium oxalate crystal growth, reduces adhesion to renal cells and induces crystal internalization into the cells, but promotes crystal aggregation.Curr. Res. Food Sci.2024810074010.1016/j.crfs.2024.10074038694557
    [Google Scholar]
  46. FerraroP.M. TaylorE.N. GambaroG. CurhanG.C. Caffeine intake and the risk of kidney stones.Am. J. Clin. Nutr.201410061596160310.3945/ajcn.114.08998725411295
    [Google Scholar]
  47. AhmedS. HasanM.M. KhanH. MahmoodZ.A. PatelS. The mechanistic insight of polyphenols in calcium oxalate urolithiasis mitigation.Biomed. Pharmacother.20181061292129910.1016/j.biopha.2018.07.08030119199
    [Google Scholar]
  48. XuX. ChenC. LiuY. MengX. CaiJ. XuR. Establishment and validation of a UPLC-MS/MS bioassay for the quantification of infigratinib in rat plasma.Arab. J. Chem.202215710389310.1016/j.arabjc.2022.10389335502159
    [Google Scholar]
  49. WangY. GuE. DuX. XuR. LinG. A novel UPLC-MS/MS assay for the measurement of linezolid and its metabolite PNU-142300 in human serum and its application to patients with renal insufficiency.Front. Pharmacol.20211264187210.3389/fphar.2021.64187234093181
    [Google Scholar]
  50. AggarwalK.P. NarulaS. KakkarM. TandonC. Nephrolithiasis: Molecular mechanism of renal stone formation and the critical role played by modulators.BioMed Res. Int.2013201312110.1155/2013/29295324151593
    [Google Scholar]
  51. UshimotoC. SugikiS. KuniiK. InoueS. KurodaE. AkaiR. IwawakiT. MiyazawaK. Dynamic change and preventive role of stress response via Keap1-Nrf2 during renal crystal formation.Free Radic. Biol. Med.202320712013210.1016/j.freeradbiomed.2023.07.01337451369
    [Google Scholar]
  52. VerkoelenC.F. Crystal retention in renal stone disease: A crucial role for the glycosaminoglycan hyaluronan?J. Am. Soc. Nephrol.20061761673168710.1681/ASN.200601008816707562
    [Google Scholar]
  53. SehakiC. JullianN. AyatiF. FernaneF. GontierE. A review of Pistacia lentiscus Polyphenols: Chemical diversity and pharmacological activities.Plants202312227910.3390/plants1202027936678991
    [Google Scholar]
  54. PohlmannA. NiendorfT. Preclinical MRI of the kidney: Methods and protocols.Springer Nature202110.1007/978‑1‑0716‑0978‑1
    [Google Scholar]
  55. MakarewiczM. DrożdżI. TarkoT. Duda-ChodakA. The interactions between polyphenols and microorganisms, especially gut microbiota.Antioxidants202110218810.3390/antiox1002018833525629
    [Google Scholar]
  56. PengQ. MaY. WangZ. WangJ. Inhibition mechanism of different structural polyphenols against α-amylase studied by solid-state NMR and molecular docking.Int. J. Biol. Macromol.2024275Pt 213375710.1016/j.ijbiomac.2024.13375738986997
    [Google Scholar]
  57. ShahidiF. DissanayakaC.S. Phenolic-protein interactions: insight from in-silico analyses: A review.Food. Product. Processing. Nutr.202351210.1186/s43014‑022‑00121‑0
    [Google Scholar]
  58. Del RioD. Rodriguez-MateosA. SpencerJ.P.E. TognoliniM. BorgesG. CrozierA. Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases.Antioxid. Redox Signal.201318141818189210.1089/ars.2012.458122794138
    [Google Scholar]
  59. SahraeianS. RashidinejadA. GolmakaniM.T. Recent advances in the conjugation approaches for enhancing the bioavailability of polyphenols.Food Hydrocoll.202414610922110.1016/j.foodhyd.2023.109221
    [Google Scholar]
  60. ThilakarathnaS. RupasingheH. Flavonoid bioavailability and attempts for bioavailability enhancement.Nutrients2013593367338710.3390/nu509336723989753
    [Google Scholar]
  61. KamilogluS. Effect of food matrix on the content and bioavailability of flavonoids.Trends Food Sci. Technol.20202117
    [Google Scholar]
  62. CostaM. Sezgin-BayindirZ. Losada-BarreiroS. Paiva-MartinsF. SasoL. Bravo-DíazC. Polyphenols as antioxidants for extending food shelf-life and in the prevention of health diseases: Encapsulation and interfacial phenomena.Biomedicines2021912190910.3390/biomedicines912190934944722
    [Google Scholar]
  63. CoryH. PassarelliS. SzetoJ. TamezM. MatteiJ. The role of polyphenols in human health and food systems: A mini-review.Front. Nutr.201858710.3389/fnut.2018.0008730298133
    [Google Scholar]
  64. AatifM. Current understanding of polyphenols to enhance bioavailability for better therapies.Biomedicines2023117207810.3390/biomedicines1107207837509717
    [Google Scholar]
  65. BertelliA. BiagiM. CorsiniM. BainiG. CappellucciG. MiraldiE. Polyphenols: From theory to practice.Foods20211011259510.3390/foods1011259534828876
    [Google Scholar]
  66. Brglez MojzerE. Knez HrnčičM. ŠkergetM. KnezŽ. BrenU. Polyphenols: Extraction methods, antioxidative action, bioavailability and anticarcinogenic effects.Molecules201621790110.3390/molecules2107090127409600
    [Google Scholar]
  67. ScheepensA. TanK. PaxtonJ.W. Improving the oral bioavailability of beneficial polyphenols through designed synergies.Genes Nutr.201051758710.1007/s12263‑009‑0148‑z19841960
    [Google Scholar]
  68. WangX. MaY. XuQ. ShikovA.N. PozharitskayaO.N. FlisyukE.V. LiuM. LiH. Vargas-MurgaL. DuezP. Flavonoids and saponins: What have we got or missed?Phytomedicine202310915458010.1016/j.phymed.2022.15458036610132
    [Google Scholar]
  69. ShabbirU. RubabM. DaliriE.B.M. ChelliahR. JavedA. OhD.H. Curcumin, quercetin, catechins and metabolic diseases: The role of gut microbiota.Nutrients202113120610.3390/nu1301020633445760
    [Google Scholar]
  70. ShangS. LiX. WangH. ZhouY. PangK. LiP. LiuX. ZhangM. LiW. LiQ. ChenX. Targeted therapy of kidney disease with nanoparticle drug delivery materials.Bioact. Mater.20243720622110.1016/j.bioactmat.2024.03.01438560369
    [Google Scholar]
  71. HanH.S. KooS.Y. ChoiK.Y. Emerging nanoformulation strategies for phytocompounds and applications from drug delivery to phototherapy to imaging.Bioact. Mater.20221418220510.1016/j.bioactmat.2021.11.02735310344
    [Google Scholar]
  72. RispoF. De Negri AtanasioG. DemoriI. CostaG. MarcheseE. Perera-del-RosarioS. Serrano-CandelasE. Palomino-SchätzleinM. PerataE. RobinoF. FerrariP.F. FerrandoS. LetasiovaS. MarkusJ. Zanotti-RussoM. GrasselliE. An extensive review on phenolic compounds and their potential estrogenic properties on skin physiology.Front. Cell Dev. Biol.202411130583510.3389/fcell.2023.130583538250328
    [Google Scholar]
  73. JiP. YuT. LiuY. JiangJ. XuJ. ZhaoY. HaoY. QiuY. ZhaoW. WuC. Naringenin-loaded solid lipid nanoparticles: Preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics.Drug Des. Devel. Ther.20161091192527041995
    [Google Scholar]
  74. MoeO.W. PearleM.S. SakhaeeK. Pharmacotherapy of urolithiasis: Evidence from clinical trials.Kidney Int.201179438539210.1038/ki.2010.38920927039
    [Google Scholar]
  75. RudrapalM. KhairnarS.J. KhanJ. DukhyilA.B. AnsariM.A. AlomaryM.N. AlshabrmiF.M. PalaiS. DebP.K. DeviR. Dietary polyphenols and their role in oxidative stress-induced human diseases: Insights into protective effects, antioxidant potentials and mechanism (s) of action.Front. Pharmacol.20221380647010.3389/fphar.2022.80647035237163
    [Google Scholar]
  76. DrydenG.W. SongM. McClainC. Polyphenols and gastrointestinal diseases.Curr. Opin. Gastroenterol.200622216517010.1097/01.mog.0000208463.69266.8c16462174
    [Google Scholar]
  77. KumarV. BansalV. MadhavanA. KumarM. SindhuR. AwasthiM.K. BinodP. SaranS. Active pharmaceutical ingredient (API) chemicals: A critical review of current biotechnological approaches.Bioengineered20221324309432710.1080/21655979.2022.203141235135435
    [Google Scholar]
/content/journals/cis/10.2174/012210299X401377251115094018
Loading
/content/journals/cis/10.2174/012210299X401377251115094018
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): Kidney stones; Metabolites; Polyphenols; Precipitation; Thermodynamics; Urolithiasis
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