Skip to main content
SpringerLink
Log in

Natural Products in the Treatment of Lower Urinary Tract Dysfunction and Infection

  • Chapter
  • First Online:
Handbook of Experimental Pharmacology

Part of the book series: Handbook of Experimental Pharmacology

Abstract

The popularity of natural products for the treatment of lower urinary tract symptoms (LUTS) differs considerably between countries. Here we discuss the clinical evidence for efficacy in two indications, male LUTS suggestive of benign prostatic hyperplasia and urinary tract infections, and the mechanistic evidence from experimental studies. Most evidence for male LUTS is based on extracts from saw palmetto berries, stinging nettle roots, and pumpkin seeds, whereas most evidence for urinary tract infection is available for European golden rod and combined preparations although this field appears more fragmented with regard to extract sources. Based on differences in sample collection and extraction, extracts from the same plants are likely to exhibit at least quantitative differences in potential active ingredients, which makes extrapolation of findings with one extract to those of others potentially difficult. While only limited information is available for most individual extracts, some extracts have been compared to placebo and/or active controls in adequately powered trials.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Addotey JN, Lengers I, Jose J, Gampe N, Beni S, Petereit F, Hensel A (2018) Isoflavonoids with inhibiting effects on human hyaluronidase-1 and norneolignan clitorienolactone B from Ononis spinosa L. root extract. Fitoterapia 130:169–174

    Google Scholar 

  • Akour A, Abuloha S, Mulakhudair AR, Kasabri V, Al-Tammemi AB (2021) Complementary and alternative medicine for urinary tract illnesses: a cross-sectional survey in Jordan. Complement Ther Clin Pract 43:101321

    Google Scholar 

  • Albrecht U, Goos KH, Schneider B (2007) A randomised, double-blind, placebo-controlled trial of a herbal medicinal product containing Tropaeoli majoris herba (Nasturtium) and Armoraciae rusticanae radix (Horseradish) for the prophylactic treatment of patients with chronically recurrent lower urinary tract infections. Curr Med Res Opin 23:2415–2422

    Google Scholar 

  • Alcaraz A, Carballido-Rodríguez J, Unda-Urzaiz M, Medina-López R, Ruiz-Cerdá JL, Rodríguez-Rubio F, García-Rojo D, Brenes-Bermúdez FJ, Cózar-Olmo JM, Baena-González V, Manasanch J (2016) Quality of life in patients with lower urinary tract symptoms associated with BPH: change over time in real-life practice according to treatment – the QUALIPROST study. Int Urol Nephrol 48:645–656

    Google Scholar 

  • Alcaraz A, Castro-Díaz D, Gacci M, Salonia A, Ficarra V, Carballido-Rodríguez J, Rodríguez-Antolín A, Medina-Polo J, Fernández-Gómez JM, Cózar-Olmo JM, Búcar-Terrades S, Pérez-León N, Brenes-Bermúdez FJ, Molero-García JM, Fernández-Pro-Ledesma A, Herdman M, Angulo JC, Manasanch J, On Behalf of the Qualiprost Study Group (2022) Efficacy and tolerability of 6-month treatment with tamsulosin plus the hexanic extract of Serenoa repens versus tamsulosin plus 5-alpha-reductase inhibitors for moderate-to-severe LUTS-BPH patients: results of a paired matched clinical study. J Clin Med 11

    Google Scholar 

  • Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Southan C, Davies JA, Abbracchio MP, Alexander W, Al-Hosaini K, Bäck M, Barnes NM, Bathgate R, Beaulieu JM, Bernstein KE, Bettler B, Birdsall NJM, Blaho V, Boulay F, Bousquet C, Bräuner-Osborne H, Burnstock G, Caló G, Castaño JP, Catt KJ, Ceruti S, Chazot P, Chiang N, Chini B, Chun J, Cianciulli A, Civelli O, Clapp LH, Couture R, Csaba Z, Dahlgren C, Dent G, Singh KD, Douglas SD, Dournaud P, Eguchi S, Escher E, Filardo EJ, Fong T, Fumagalli M, Gainetdinov RR, Gasparo M, Gerard C, Gershengorn M, Gobeil F, Goodfriend TL, Goudet C, Gregory KJ, Gundlach AL, Hamann J, Hanson J, Hauger RL, Hay DL, Heinemann A, Hollenberg MD, Holliday ND, Horiuchi M, Hoyer D, Hunyady L, Husain A, AP IJ, Inagami T, Jacobson KA, Jensen RT, Jockers R, Jonnalagadda D, Karnik S, Kaupmann K, Kemp J, Kennedy C, Kihara Y, Kitazawa T, Kozielewicz P, Kreienkamp HJ, Kukkonen JP, Langenhan T, Leach K, Lecca D, Lee JD, Leeman SE, Leprince J, Li XX, Williams TL, Lolait SJ, Lupp A, Macrae R, Maguire J, Mazella J, McArdle CA, Melmed S, Michel MC, Miller LJ, Mitolo V, Mouillac B, Müller CE, Murphy P, Nahon JL, Ngo T, Norel X, Nyimanu D, O’Carroll AM, Offermanns S, Panaro MA, Parmentier M, Pertwee RG, Pin JP, Prossnitz ER, Quinn M, Ramachandran R, Ray M, Reinscheid RK, Rondard P, Rovati GE, Ruzza C, Sanger GJ, Schöneberg T, Schulte G, Schulz S, Segaloff DL, Serhan CN, Stoddart LA, Sugimoto Y, Summers R, Tan VP, Thal D, Thomas WW, Timmermans P, Tirupula K, Tulipano G, Unal H, Unger T, Valant C, Vanderheyden P, Vaudry D, Vaudry H, Vilardaga JP, Walker CS, Wang JM, Ward DT, Wester HJ, Willars GB, Woodruff TM, Yao C, Ye RD (2021) The concise guide to pharmacology 2021/22: G protein-coupled receptors. Br J Pharmacol 178(Suppl 1):S27–S156

    Google Scholar 

  • Bach D (2000) Placebokontrollierte Langzeittherapiestudie mit Kürbissamenextrakt bei BPH-bedingten Miktionsbeschwerden. Urologe B 40:437–443

    Google Scholar 

  • Barry MJ, Williford WO, Chang Y, Machi M, Jones KM, Walker-Corkery E, Lepor H (1995) Benign prostatic hyperplasia specific healthy status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic Hyerplasia impact index is perceptible to patients? J Urol 154:1770–1774

    Google Scholar 

  • Barry MJ, Meleth S, Lee JY, Kreder KJ, Avins AL, Nickel JC, Roehrborn CG, Crawford ED, Foster HE Jr, Kaplan SA, McCullough A, Andriole GL, Naslund MJ, Williams OD, Kusek JW, Meyers CM, Betz JM, Cantor A, McVary KT (2011) Effects of increasing doses of saw palmetto extract on lower urinary tract symptoms. A randomized trial. J Am Med Assoc 306:1344–1351

    Google Scholar 

  • Bazydlo-Guzenda K, Buda P, Matloka M, Mach M, Stelmach F, Dzida R, Smuga D, Hucz-Kalitowska J, Teska-Kaminska M, Vialichka V, Dubiel K, Kaminska B, Wieczorek M, Pieczykolan J (2021) CPL207280, a novel G protein–coupled receptor 40/free fatty acid receptor 1–specific agonist, shows a favorable safety profile and exerts antidiabetic effects in type 2 diabetic animals. Mol Pharmacol 100:335–347

    Google Scholar 

  • Bent S, Kane C, Shinohara K, Neuhaus J, Hudes ES, Goldberg H, Avins AL (2006) Saw palmetto for benign prostatic hyperplasia. N Engl J Med 354:335–566

    Google Scholar 

  • Berges RR, Windeler J, Trampisch HJ, Senge T (1995) Randomised, double-blind clinical trial of ß-sitosterol in patients with benign prostatic hyperplasia. Lancet 354:1529–1532

    Google Scholar 

  • Berges RR, Kassen A, Senge T (2000) Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18-month follow-up. BJU Int 85:842–846

    Google Scholar 

  • Berges RR, Pientka L, Höfner K, Senge T, Jonas U (2001) Male lower urinary tract symptoms and related health care seeking in Germany. Eur Urol 39:682–687

    Google Scholar 

  • Bondarenko B, Walther C, Funk P, Schläfke S, Engelmann U (2003) Long-term efficacy and safety of PRO 160/120 (a combination of sabal and urtica extract) in patients with lower urinary tract symptoms (LUTS). Phytomedicine 10(Suppl 4):53–55

    Google Scholar 

  • Borchert VE, Czyborra P, Fetscher C, Goepel M, Michel MC (2004) Extracts from Rhois aromatica and Solidaginis vigaurea inhibit rat and human bladder contraction. Naunyn Schmiedebergs Arch Pharmacol 369:281–286

    Google Scholar 

  • Buck AC (2004) Is there a scientific basis for the therapeutic effects of Serenoa repens in benign prostatic hyperplasia? Mechanisms of action. J Urol 172:1792–1799

    Google Scholar 

  • Carraro JC, Raynaud JP, Koch G, Chisholm GD, Di Silverio F, Teillac P, Da Silva FC, Cauquil J, Chopin DK, Hamdy FC, Hanus M, Hauri D, Kalinteris A, Marencak J, Perier A, Perrin P (1996) Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Prostate 29:231–240. discussion 241–232

    Google Scholar 

  • Chatelain C, World Health Organization, Organització Mundial de la Salut, International Union against Cancer, International Consultation on Benign Prostatic Hyperplasia and Unión Internacional contra el Cáncer (2001) Benign prostatic hyperplasia: 5th international consultation on benign prostatic hyperplasia (BPH) – June 25–28, 2000, Health Publication Limited, Paris

    Google Scholar 

  • Chda A, Kabbaoui M, Chokri A, Abida K, Tazi A, Cheikh R (2016) Spasmolytic action of Centaurium erythraea on rabbit jejunum is through Calcium Channel blockade and NO release. Eur J Med Plants 11:1–13

    Google Scholar 

  • Ci X, Zhou J, Lv H, Yu Q, Peng L, Hua S (2017) Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism. Cell Death Dis 8:e2798

    Google Scholar 

  • Conrad A, Kolberg T, Engels I, Frank U (2006) In vitro study to evaluate the antibacterial activity of a combination of the haulm of nasturtium (Tropaeoli majoris herba) and of the roots of horseradish (Armoraciae rusticanae radix). Arzneimittelforschung 56:842–849

    Google Scholar 

  • Cornu JN, Cussenot O, Haab F, Lukacs B (2010) A widespread population study of actual management of lower urinary tract symptoms related to benign prostatic hyperplasia across Europe and beyond official clinical guidelines. Eur Urol 58:450–456

    Google Scholar 

  • Csikós E, Horváth A, Ács K, Papp N, Balázs VL, Dolenc MS, Kenda M, Kočevar Glavač N, Nagy M, Protti M, Mercolini L, Horváth G, Farkas Á, On Behalf of the Oemonom (2021) Treatment of benign prostatic hyperplasia by natural drugs. Molecules 26

    Google Scholar 

  • Cunha BA (2001) Antibiotic side effects. Med Clin North Am 85:149–185

    Google Scholar 

  • Daoutidou M, Plessas S, Alexopoulos A, Mantzourani I (2021) Assessment of antimicrobial activity of pomegranate, cranberry, and black chokeberry extracts against foodborne pathogens. Food Secur 10

    Google Scholar 

  • de Arriba SG, Naser B, Nolte KU (2013) Risk assessment of free hydroquinone derived from Arctostaphylos Uva-ursi folium herbal preparations. Int J Toxicol 32:442–453

    Google Scholar 

  • De Monte C, Carradori S, Granese A, Di Pierro GB, Leonardo C, De Nunzio C (2014) Modern extraction techniques and their impact on the pharmacological profile of Serenoa repens extracts for the treatment of lower urinary tract symptoms. BMC Urol 14:63

    Google Scholar 

  • de Oliveira JR, Camargo SEA, de Oliveira LD (2019) Rosmarinus officinalis L. (rosemary) as therapeutic and prophylactic agent. J Biomed Sci 26:5

    Google Scholar 

  • Debruyne F, Koch G, Boyle P, Da Silva FC, Gillenwater JY, Hamdy FC, Perrin P, Teillac P, Vela-Navarrete R, Raynaud JP (2002) Comparison of a phytotherapeutic agent (Permixon) with an α-blocker (tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study. Eur Urol 41:497–507

    Google Scholar 

  • Deipenbrock M, Sendker J, Hensel A (2020) Aqueous root extract from Ononis spinosa exerts anti-adhesive activity against Uropathogenic Escherichia coli. Planta Med 86:247–254

    Google Scholar 

  • DGU (2017) Interdisziplinäre S3 Leitlinie: Epidemiologie, Diagnostik, Therapie, Prävention und Management unkomplizierter, bakterieller, ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten, Langversion 1.1-2, AWMF Registernummer: 043/044

    Google Scholar 

  • Dreikorn K, Lowe FC, Borkowski A, Buck C, Braeckman J, Chopin D, Denis L, Ferrari P, Habib FK, Perrin P (2001) Other medical therapies. In: Chatelain C, Denis L, Foo KT, Khoury S, McConnel JD (eds) Benign prostatic hyperplasia. Plymbridge Distributors Ltd, Plymouth, pp 479–511

    Google Scholar 

  • Efferth T, Oesch F (2022) Anti-inflammatory and anti-cancer activities of frankincense: targets, treatments and toxicities. Semin Cancer Biol 80:39–57

    Google Scholar 

  • Eichel V, Schuller A, Biehler K, Al-Ahmad A, Frank U (2020) Antimicrobial effects of mustard oil-containing plants against oral pathogens: an in vitro study. BMC Complement Med Ther 20:156

    Google Scholar 

  • El Menyiy N, Guaouguaou FE, El Baaboua A, El Omari N, Taha D, Salhi N, Shariati MA, Aanniz T, Benali T, Zengin G, El-Shazly M, Chamkhi I, Bouyahya A (2021) Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn. J Ethnopharmacol 276:114171

    Google Scholar 

  • Engelmann U, Walther C, Bondarenko B, Funk P, Schläfke S (2006) Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin. Arzneimittelforschung 56:222–229

    Google Scholar 

  • European Medicines Agency (2001) Herbal medicinal products

    Google Scholar 

  • European Medicines Agency (2004) Committee on Herbal Medicinal Products (HMPC)

    Google Scholar 

  • European Medicines Agency (2015a) Assessment report on Serenoa repens (W. Bartram) Small, frcutus

    Google Scholar 

  • European Medicines Agency (2015b) Overview of comments received on European Union hebal monograph on Serenoa repens (W. Bartram) Small, fructors (EMA/HPMC/280079/2013), European Medicines Agency

    Google Scholar 

  • Feliciano RP, Mills CE, Istas G, Heiss C, Rodriguez-Mateos A (2017) Absorption, metabolism and excretion of cranberry (poly)phenols in humans: a dose response study and assessment of inter-individual variability. Nutrients 9

    Google Scholar 

  • Flower A, Wang LQ, Lewith G, Liu JP, Li Q (2015) Chinese herbal medicine for treating recurrent urinary tract infections in women. Cochrane Database Syst Rev 2015:CD010446

    Google Scholar 

  • Fornara P, Madersbacher S, Vahlensieck W, Bracher F, Romics I, Kil P (2020) Phytotherapy adds to the therapeutic armamentarium for the treatment of mild-to-moderate lower urinary tract symptoms in men. Urol Int 104:333–342

    Google Scholar 

  • Frumenzio E, Maglia D, Salvini E, Giovannozzi S, Di Biase M, Bini V, Costantini E (2013) Role of phytotherapy associated with antibiotic prophylaxis in female patients with recurrent urinary tract infections. Arch Ital Urol Androl 85:197–199

    Google Scholar 

  • Fu Z, Liska D, Talan D, Chung M (2017) Cranberry reduces the risk of urinary tract infection recurrence in otherwise healthy women: a systematic review and meta-analysis. J Nutr 147:2282–2288

    Google Scholar 

  • Fursenco C, Calalb T, Uncu L, Dinu M, Ancuceanu R (2020) Solidago virgaurea L.: a review of its Ethnomedicinal uses, Phytochemistry, and pharmacological activities. Biomol Ther 10

    Google Scholar 

  • Gagyor I, Hummers E, Schmiemann G, Friede T, Pfeiffer S, Afshar K, Bleidorn J (2021) Herbal treatment with uva ursi extract versus fosfomycin in women with uncomplicated urinary tract infection in primary care: a randomized controlled trial. Clin Microbiol Infect 27:1441–1447

    Google Scholar 

  • Gampe N, Szakacs Z, Darcsi A, Boldizsar I, Szoke E, Kuzovkina I, Kursinszki L, Beni S (2020) Qualitative and quantitative phytochemical analysis of Ononis hairy root cultures. Front Plant Sci 11:622585

    Google Scholar 

  • Gbinigie OA, Spencer EA, Heneghan CJ, Lee JJ, Butler CC (2020) Cranberry extract for symptoms of acute, uncomplicated urinary tract infection: a systematic review. Antibiotics (Basel) 10

    Google Scholar 

  • Genovese C, Davinelli S, Mangano K, Tempera G, Nicolosi D, Corsello S, Vergalito F, Tartaglia E, Scapagnini G, Di Marco R (2018) Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections. J Chemother 30:107–114

    Google Scholar 

  • Goepel M, Hecker U, Krege S, Rübben H, Michel MC (1999) Saw palmetto extracts potently and noncompetitively inhibit human α1-adrenoceptors in vitro. Prostate 38:208–215

    Google Scholar 

  • Goepel M, Dinh L, Mitchell A, Schäfers RF, Rübben H, Michel MC (2001) Do saw palmetto extracts block human α1-adrenoceptor subtypes in vivo? Prostate 46:226–232

    Google Scholar 

  • Gonzalez de Llano D, Liu H, Khoo C, Moreno-Arribas MV, Bartolome B (2019) Some new findings regarding the antiadhesive activity of cranberry phenolic compounds and their microbial-derived metabolites against Uropathogenic bacteria. J Agric Food Chem 67:2166–2174

    Google Scholar 

  • Gonzalez de Llano D, Moreno-Arribas MV, Bartolome B (2020) Cranberry polyphenols and prevention against urinary tract infections: relevant considerations. Molecules 25

    Google Scholar 

  • Gossell-Williams M, Davis A, O'Connor N (2006) Inhibition of testosterone-induced hyperplasia of the prostate of Sprague-Dawley rats by pumpkin seed oil. J Med Food 9:284–286

    Google Scholar 

  • Gravas S, Cornu JN, Gacci M, Gratzke C, Herrmann TRW, Mamoulakis C, Rieken M, Speakman M, Tikkinen KA (2022) Management of non-neurogenic male LUTS. Eur Assoc Urol

    Google Scholar 

  • Habib FK, Wyllie MG (2004) Not all brands are created equal: a comparison of selected components of different brands of Serenoa repens extract. Prostate Cancer Prostatic Dis 7:195–200

    Google Scholar 

  • Herz C, Tran HT, Marton MR, Maul R, Baldermann S, Schreiner M, Lamy E (2017) Evaluation of an aqueous extract from horseradish root (Armoracia rusticana Radix) against lipopolysaccharide-induced cellular inflammation reaction. Evid Based Complement Alternat Med 2017:1950692

    Google Scholar 

  • Holler M, Steindl H, Abramov-Sommariva D, Wagenlehner F, Naber KG, Kostev K (2021) Treatment of urinary tract infections with Canephron((R)) in Germany: a retrospective database analysis. Antibiotics (Basel) 10

    Google Scholar 

  • Irwin DE, Milsom I, Kopp Z, Abrams P (2008) Symptom bother and health care-seeking behavior among individuals with overactive bladder. Eur Urol 53:1029–1039

    Google Scholar 

  • Jepson RG, Williams G, Craig JC (2012) Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 10:CD001321

    Google Scholar 

  • Kassen A, Berges R, Senge T (2000) Effect of beta-sitosterol on transforming growth factor-beta-1 expression and translocation protein kinase C alpha in human prostate stromal cells in vitro. Eur Urol 37:735–741

    Google Scholar 

  • Keehn A, Taylor J, Lowe FC (2016) Phytotherapy for benign prostatic hyperplasia. Curr Urol Rep 17:53

    Google Scholar 

  • Klippel KF, Hiltl DM, Schipp B (1997) A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto study group. Br J Urol 80:427–432

    Google Scholar 

  • Koch E (2001) Extracts from fruits of saw palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms. Planta Med 67:489–500

    Google Scholar 

  • Kranz J, Lackner J, Künzel U, Wagenlehner F, Schmidt S (2022) Phytotherapy in adults with recurrent uncomplicated cystitis. Dtsch Arztebl Int 119:353–360

    Google Scholar 

  • Kwok M, McGeorge S, Mayer-Coverdale J, Graves B, Paterson DL, Harris PNA, Esler R, Dowling C, Britton S, Roberts MJ (2022) Guideline of guidelines: management of recurrent urinary tract infections in women. BJU Int 130(Suppl 3):11–22

    Google Scholar 

  • Latil A, Pétrissans MT, Rouquet J, Robert G, de la Taille A (2015) Effects of hexanic extract of Serenoa repens (Permixon® 160 mg) on inflammation biomarkers in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Prostate 75:1857–1867

    Google Scholar 

  • Lee YL, Najm WI, Owens J, Thrupp L, Baron S, Shanbrom E, Cesario T (2010) Anti-microbial activity of urine after ingestion of cranberry: a pilot study. Evid Based Complement Alternat Med 7:227–232

    Google Scholar 

  • Liu H, Howell AB, Zhang DJ, Khoo C (2019) A randomized, double-blind, placebo-controlled pilot study to assess bacterial anti-adhesive activity in human urine following consumption of a cranberry supplement. Food Funct 10:7645–7652

    Google Scholar 

  • Lopatkin N, Sivkov A, Walther C, Schläfke S, Medvedev A, Avdeichuk J, Golubev G, Melnik K, Elenberger N, Engelmann U (2005) Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms – a placebo-controlled, double-blind, multicenter trial. World J Urol 23:139–146

    Google Scholar 

  • Lopatkin N, Sivkov A, Schläfke S, Funk P, Medvedev A and Engelmann U (2007) Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms – long-term follow-up of a placebo-controlled, double-blind, multicenter trial. Int Urol Nephrol 39:1137–1146

    Google Scholar 

  • Marcon J, Schubert S, Stief CG, Magistro G (2019) In vitro efficacy of phytotherapeutics suggested for prevention and therapy of urinary tract infections. Infection 47:937–944

    Google Scholar 

  • McConnell JD, Roehrborn CG, Bautista O, Andriole GL, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg LM, Clarke HS, Crawford ED, Diokno AC, Foley JP, Foster HE, Jacobs SC, Kaplan SA, Kreder KJ, Lieber MM, Lucia MS, Miller GJ, Menon M, Milam DF, Ramsdell JW, Schenkman NS, Slawin KM, Smith JA (2003) The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 349:2387–2398

    Google Scholar 

  • Mekinic IG, Skroza D, Ljubenkov I, Katalinic V, Simat V (2019) Antioxidant and antimicrobial potential of phenolic metabolites from traditionally used Mediterranean herbs and spices. Food Secur 8

    Google Scholar 

  • Metzker H, Kieser M, Hölscher U (1996) Wirksamkeit eines Sabal-Urtica-Kombinationspräparats bei der Behandlung der benignen Prostatahyperplasie (BPH). Der Urologe B 36:292–300

    Google Scholar 

  • Mitroupoulos D, Anastasiou I, Giannopoulo C, Nikolopoulos G, Alamanis C, Zervas A (2002) Symptomatic benign prostatic hyperplasia: impact on partners’ quality of life. Eur Urol 41:240–245

    Google Scholar 

  • Monroy-Torres R, Macías A (2005) Does cranberry juice have bacteriostatic activity? Rev Invest Clin 57:442–446

    Google Scholar 

  • Moore M, Trill J, Simpson C, Webley F, Radford M, Stanton L, Maishman T, Galanopoulou A, Flower A, Eyles C, Willcox M, Hay AD, van der Werf E, Gibbons S, Lewith G, Little P, Griffiths G (2019) Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial. Clin Microbiol Infect 25:973–980

    Google Scholar 

  • Mutters NT, Mampel A, Kropidlowski R, Biehler K, Gunther F, Balu I, Malek V, Frank U (2018) Treating urinary tract infections due to MDR E. coli with Isothiocyanates – a phytotherapeutic alternative to antibiotics? Fitoterapia 129:237–240

    Google Scholar 

  • Nausch B, Pace S, Pein H, Koeberle A, Rossi A, Kunstle G, Werz O (2019) The standardized herbal combination BNO 2103 contained in Canephron((R)) N alleviates inflammatory pain in experimental cystitis and prostatitis. Phytomedicine 60:152987

    Google Scholar 

  • Nausch B, Bittner CB, Holler M, Abramov-Sommariva D, Hiergeist A, Gessner A (2022) Contribution of symptomatic, herbal treatment options to antibiotic stewardship and microbiotic health. Antibiotics (Basel):11

    Google Scholar 

  • Ngalah BS, Borner K, Kropidlowsky M, Finkbeiner J, Harter A, Biehler K, Frank U (2022) Combination of isothiocyanates and antibiotics increases susceptibility against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Serratia marcescens. Fitoterapia:105382

    Google Scholar 

  • Novara G, Giannarini G, Alcaraz A, Cózar-Olmo JM, Descazeaud A, Montorsi F, Ficarra V (2016) Efficacy and safety of hexanic lipidosterolic extract of Serenoa repens (Permixon) in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. Eur Urol Focus 2:553–561

    Google Scholar 

  • Oelke M, Berges R, Schläfke S, Burkart M (2014) Fixed-dose combination PRO 160/120 of sabal and urtica extracts improves nocturia in men with LUTS suggestive of BPH: re-evaluation of four controlled clinical studies. World J Urol 32:1149–1154

    Google Scholar 

  • Onuska NPR, Pierce JG (2022) Synthesis reveals unexpected biological targets of a traditional medicine. Nature 606:869–870

    Google Scholar 

  • Ostlund RE Jr, McGill JB, Zeng CM, Covey DF, Stearns J, Stenson WF, Spilburg CA (2002) Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans. Am J Physiol Endocrinol Metab 282:E911–E916

    Google Scholar 

  • Pigat N, Reyes-Gomez E, Boutillon F, Palea S, Barry Delongchamps N, Koch E, Goffin V (2019) Combined sabal and urtica extracts (WS® 1541) exert anti-proliferative and anti-inflammatory effects in a mouse model of benign prostate hyperplasia. Front Pharmacol 10:311

    Google Scholar 

  • Quintus J, Kovar KA, Link P, Hamacher H (2005) Urinary excretion of arbutin metabolites after oral administration of bearberry leaf extracts. Planta Med 71:147–152

    Google Scholar 

  • Rasanen RM, Hieta JP, Immanen J, Nieminen K, Haavikko R, Yli-Kauhaluoma J, Kauppila TJ (2019) Chemical profiles of birch and alder bark by ambient mass spectrometry. Anal Bioanal Chem 411:7573–7583

    Google Scholar 

  • Riaz G, Chopra R (2018) A review on phytochemistry and therapeutic uses of Hibiscus sabdariffa L. Biomed Pharmacother 102:575–586

    Google Scholar 

  • Ritschel WA, Kastner U, Hussain AS, Koch HP (1990) Pharmacokinetics and bioavailability of beta-sitosterol in the beagle dog. Arzneimittelforschung 40:463–468

    Google Scholar 

  • Russo GI, Scandura C, Di Mauro M, Cacciamani G, Albersen M, Hatzichristodoulou G, Fode M, Capogrosso P, Cimino S, Marcelissen T, Cornu JN, Gacci M, Minervini A, Cocci A (2021) Clinical efficacy of serenoa repens versus placebo versus alpha-blockers for the treatment of lower urinary tract symptoms/benign prostatic enlargement: a systematic review and network meta-analysis of randomized placebo-controlled clinical trials. Eur Urol Focus 7:420–431

    Google Scholar 

  • Safarinejad MR (2005) Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study. J Herb Pharmacother 5:1–11

    Google Scholar 

  • Samoilova Z, Muzyka N, Lepekhina E, Oktyabrsky O, Smirnova G (2014) Medicinal plant extracts can variously modify biofilm formation in Escherichia coli. Antonie Van Leeuwenhoek 105:709–722

    Google Scholar 

  • Scaglione F (2015) How to choose the right Serenoa repens extract. Eur Urol Suppl 14:e1464–e1469

    Google Scholar 

  • Scaglione F, Lucini V, Pannacci M, Caronno A, Leone C (2008) Comparison of the potency of different brands of Serenoa repens extract on 5alpha-reductase types I and II in prostatic co-cultured epithelial and fibroblast cells. Pharmacology 82:270–275

    Google Scholar 

  • Schindler G, Patzak U, Brinkhaus B, von Niecieck A, Wittig J, Krahmer N, Glockl I, Veit M (2002) Urinary excretion and metabolism of arbutin after oral administration of Arctostaphylos uvae ursi extract as film-coated tablets and aqueous solution in healthy humans. J Clin Pharmacol 42:920–927

    Google Scholar 

  • Schneider T, Rübben H (2004) Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS). Results of a randomized, double-blind, placebo controlled multicenter study after 12 months. Urologe A 43:302–306

    Google Scholar 

  • Sharma M, Chadha R, Dhingra N (2017) Phytotherapeutic agents for benign prostatic hyperplasia: an overview. Mini Rev Med Chem 17:1346–1363

    Google Scholar 

  • Sihra N, Goodman A, Zakri R, Sahai A, Malde S (2018) Nonantibiotic prevention and management of recurrent urinary tract infection. Nat Rev Urol 15:750–776

    Google Scholar 

  • Skrovankova S, Sumczynski D, Mlcek J, Jurikova T, Sochor J (2015) Bioactive compounds and antioxidant activity in different types of berries. Int J Mol Sci 16:24673–24706

    Google Scholar 

  • Sökeland J, Albrecht J (1997) Kombination aus Sabal- und Urticaextrakt vs. Finasterid bei BPH (Stad. I bis II nach Alken). Vergleich der therapeutischen Wirksamkeit in einer einjährigen Doppelblindstudie. Urologe A 36:327–333

    Google Scholar 

  • Sperling H, Lorenz A, Krege S, Arndt R, Michel MC (2002) An extract from the bark of Aspidosperma quebracho blanco binds to human penile α-adrenoceptors. J Urol 168:160–163

    Google Scholar 

  • Spiegler V, Gierlikowska B, Saenger T, Addotey JN, Sendker J, Jose J, Kiss AK, Hensel A (2020) Root extracts from Ononis spinosa inhibit IL-8 release via interactions with toll-like receptor 4 and lipopolysaccharide. Front Pharmacol 11:889

    Google Scholar 

  • Tacklind J, Macdonald R, Rutks I, Stanke JU, Wilt TJ (2012) Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev 12:Cd001423

    Google Scholar 

  • Tamalunas A, Wendt A, Springer F, Vigodski V, Ciotkowska A, Rutz B, Wang R, Huang R, Liu Y, Schulz H, Ledderose S, Kolben T, Magistro G, Stief CG, Hennenberg M (2022) Permixon®, hexane-extracted Serenoa repens, inhibits human prostate and bladder smooth muscle contraction and exerts growth-related functions in human prostate stromal cells. Life Sci 308:120931

    Google Scholar 

  • Tolmacheva AA, Rogozhin EA, Deryabin DG (2014) Antibacterial and quorum sensing regulatory activities of some traditional eastern-European medicinal plants. Acta Pharm 64:173–186

    Google Scholar 

  • Tran HT, Marton MR, Herz C, Maul R, Baldermann S, Schreiner M, Lamy E (2016) Nasturtium (Indian cress, Tropaeolum majus nanum) dually blocks the COX and LOX pathway in primary human immune cells. Phytomedicine 23:611–620

    Google Scholar 

  • Tsai YS, Tong YC, Cheng JT, Lee CH, Yang FS, Lee HY (2006) Pumpkin seed oil and phytosterol-F can block testosterone/prazosin-induced prostate growth in rats. Urol Int 77:269–274

    Google Scholar 

  • Vahlensieck W, Theurer C, Pfitzer E, Patz B, Banik N, Engelmann U (2015) Effects of pumpkin seed in men with lower urinary tract symptoms due to benign prostatic hyperplasia in the one-year, randomized, placebo-controlled GRANU study. Urol Int 94:286–295

    Google Scholar 

  • Vahlensieck W, Lorenz H, Schumacher-Stimpfl A, Fischer R, Naber KG (2019) Effect of a herbal therapy on clinical symptoms of acute lower uncomplicated urinary tract infections in women: secondary analysis from a randomized controlled trial. Antibiotics (Basel) 8

    Google Scholar 

  • Vela-Navarrete R, Alcaraz A, Rodríguez-Antolín A, Miñana López B, Fernández-Gómez JM, Angulo JC, Castro Díaz D, Romero-Otero J, Brenes FJ, Carballido J, Molero García JM, Fernández-Pro Ledesma A, Cózar Olmos JM, Manasanch Dalmau J, Subirana Cachinero I, Herdman M, Ficarra V (2018) Efficacy and safety of a hexanic extract of Serenoa repens (Permixon(®) ) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis of randomised controlled trials and observational studies. BJU Int 122:1049–1065

    Google Scholar 

  • Wagenlehner FM, Abramov-Sommariva D, Holler M, Steindl H, Naber KG (2018) Non-antibiotic herbal therapy (BNO 1045) versus antibiotic therapy (Fosfomycin trometamol) for the treatment of acute lower uncomplicated urinary tract infections in women: a double-blind, parallel-group, randomized, multicentre, non-inferiority phase III trial. Urol Int 101:327–336

    Google Scholar 

  • Witteman L, van Wietmarschen HA, van der Werf ET (2021) Complementary medicine and self-care strategies in women with (recurrent) urinary tract and vaginal infections: a cross-sectional study on use and perceived effectiveness in The Netherlands. Antibiotics (Basel) 10

    Google Scholar 

  • Wojnicz D, Kucharska AZ, Sokol-Letowska A, Kicia M, Tichaczek-Goska D (2012) Medicinal plants extracts affect virulence factors expression and biofilm formation by the uropathogenic Escherichia coli. Urol Res 40:683–697

    Google Scholar 

  • Wojnicz D, Tichaczek-Goska D, Glensk M, Hendrich AB (2021) Is it worth combining Solidago virgaurea extract and antibiotics against uropathogenic Escherichia coli rods? An in vitro model study. Pharmaceutics 13

    Google Scholar 

  • Xia JY, Yang C, Xu DF, Xia H, Yang LG, Sun GJ (2021) Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: a systematic review and meta-analysis with trial sequential analysis. PLoS One 16:e0256992

    Google Scholar 

  • Zhang B, Zeng M, Li B, Kan Y, Wang S, Cao B, Huang Y, Zheng X, Feng W (2021) Arbutin attenuates LPS-induced acute kidney injury by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway. Phytomedicine 82:153466

    Google Scholar 

  • Zimmerman RA, Thompson IM Jr (2002) Prevalence of complementary medicine in urologic practice. A review of recent studies with emphasis on use among prostate cancer patients. Urol Clin North Am 29:1–9. vii

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General, Visceral and Transplant Surgery, University Medical Center, Johannes Gutenberg University, Mainz, Germany

    Ann-Kathrin Lederer

  2. Center for Complementary Medicine, Department of Medicine II, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Freiburg, Germany

    Ann-Kathrin Lederer

  3. Department of Pharmacology, University Medical Center, Johannes Gutenberg University, Mainz, Germany

    Martin C. Michel

Authors
  1. Ann-Kathrin Lederer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin C. Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin C. Michel .

Ethics declarations

Research related to lower urinary tract in the lab of MCM is funded in part by Deutsche Forschungsgemeinschaft (Mi 294/10-1), Apogepha Arzneimittel GmbH (Dresden, Germany), and Stiftung Männergesundheit (Berlin, Germany).

The medical departments of Apogepha, Bionorica, Dr. Willmar Schwabe, and Pierre Fabre have assisted in the literature search for this manuscript; they were not involved in the writing of this manuscript.

Conflict of Interest

AKL declares no conflict of interest.

MCM has received research funding, consultancy, and/or lecturer honoraria from Apogepha, Astellas, Dr. Willmar Schwabe, GSK, Sanofi-Aventis, and Stiftung Männergesundheit.

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lederer, AK., Michel, M.C. (2024). Natural Products in the Treatment of Lower Urinary Tract Dysfunction and Infection. In: Handbook of Experimental Pharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/164_2024_708

Download citation

  • DOI: https://doi.org/10.1007/164_2024_708

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

Publish with us

Policies and ethics

Search

Navigation