{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:13:06Z","timestamp":1792692786167,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: This study aimed to compare the effects and safety of boldine combined with Phyllanthus niruri and Ononis spinosa plus tamsulosin vs. tamsulosin alone in medical expulsive therapy (MET) for distal ureteral calculi. Materials and Methods: This retrospective cohort study was conducted on 159 renal colic patients with distal ureteric stones (\u226410 mm). Patients aged between 18 and 70 years or older with distal ureteral (below the sacroiliac joint) stones \u226410 mm (defined by the largest diameter in three planes) confirmed by urinary ultrasonography and\/or native computed tomography (CT). Patients were divided into two groups: A and B. Patients in Group A received tamsulosin 0.4 mg plus boldine combined with Phyllanthus niruri and Ononis spinosa, while those in Group B received tamsulosin 0.4 mg. The rate of stone expulsion, duration of stone expulsion, the dose and the duration of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesic use, and adverse effects of drugs were recorded. Results: No differences were reported in demographic profiles between the two groups. The stone expulsion rate in Group A (84.8%) was higher in comparison to Group B (52.5%); the mean time of stone expulsion was 16.33 \u00b1 4.75 days in Group A and 19.33 \u00b1 6.42 days in Group B. The mean requirement time of analgesia was significantly less in Group A, 2.42 \u00b1 2.56, than in Group B, 6.25 \u00b1 3.05. Drug-related adverse effects (headache, dizziness, nausea, vomiting, postural hypotension, backache, and running nose) were comparable between the two groups. Conclusions: Tamsulosin plus boldine combined with Phyllanthus niruri and Ononis spinosa as medical expulsion therapy is more effective for distal ureteric stones with less need for analgesics and a shorter stone expulsion time than tamsulosin alone.<\/jats:p>","DOI":"10.3390\/medicina60091455","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T06:44:29Z","timestamp":1725518669000},"page":"1455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and Safety of Boldine Combined with Phyllanthus\u00a0niruri and Ononis spinosa in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Single-Center, Retrospective Cohort Study"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0552-4829","authenticated-orcid":false,"given":"Ernesto","family":"Di Mauro","sequence":"first","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Saldutto","sequence":"additional","affiliation":[{"name":"Department of Urology, Humanitas Gavazzeni, 24125 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"La Rocca","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5862-1967","authenticated-orcid":false,"given":"Giuseppe","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Patelli","sequence":"additional","affiliation":[{"name":"Radiology Department, ASST Bergamo Est, 24068 Seriate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-132X","authenticated-orcid":false,"given":"Biagio","family":"Barone","sequence":"additional","affiliation":[{"name":"Department of Urology, Ospedale del Mare, ASL NA1 Centro, 80147 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-9024","authenticated-orcid":false,"given":"Vittore","family":"Verratti","sequence":"additional","affiliation":[{"name":"Department of Psychological, Health and Territorial Sciences, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-5822","authenticated-orcid":false,"given":"Roberto","family":"Castellucci","sequence":"additional","affiliation":[{"name":"Department of Urology, SS. Annunziata Hospital, ASL 2 Abruzzo, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-0356","authenticated-orcid":false,"given":"Luigi","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Urology Unit, Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Iacono","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u201cV. Tiberio\u201d, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo Maria","family":"Altieri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u201cV. Tiberio\u201d, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.2147\/CLEP.S370591","article-title":"Global, Regional, and National Burden of Urolithiasis from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"15","author":"Zhang","year":"2022","journal-title":"Clin Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1080\/07853890.2022.2085882","article-title":"Sex disparities and the risk of urolithiasis: A large cross-sectional study","volume":"54","author":"Xu","year":"2022","journal-title":"Ann. Med."},{"key":"ref_3","first-page":"19086","article-title":"Efficacy of silodosin in the treatment of distal ureteral stones 4 to 10 mm in diameter","volume":"8","author":"Yuksel","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1097\/00005392-199909010-00014","article-title":"Time to stone passage for observed ureteral calculi: A guide for patient education","volume":"162","author":"Miller","year":"1999","journal-title":"J. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wu, Y.C., Hou, C.P., and Weng, S.C. (2023). Lifestyle and Diet as Risk Factors for Urinary Stone Formation: A Study in a Taiwanese Population. Medicina, 59.","DOI":"10.3390\/medicina59111895"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ferraro, P.M., Bargagli, M., Trinchieri, A., and Gambaro, G. (2020). Risk of Kidney Stones: Influence of Dietary Factors, Dietary Patterns, and Vegetarian-Vegan Diets. Nutrients, 12.","DOI":"10.3390\/nu12030779"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Khalili, P., Jamali, Z., Sadeghi, T., Esmaeili-Nadimi, A., Mohamadi, M., Moghadam-Ahmadi, A., Ayoobi, F., and Nazari, A. (2021). Risk factors of kidney stone disease: A cross-sectional study in the southeast of Iran. BMC Urol., 21.","DOI":"10.1186\/s12894-021-00905-5"},{"key":"ref_8","first-page":"11076","article-title":"Mobile health applications in kidney stone disease management: A reliable support for patients?","volume":"95","author":"Cirillo","year":"2023","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_9","first-page":"227","article-title":"Minimally Invasive Surgery for the Treatment of Ureteric Stones-State-of-the-Art Review","volume":"13","author":"Bhanot","year":"2021","journal-title":"Res. Rep. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1590\/s1677-5538.ibju.2023.0345","article-title":"Tamsulosin vs. Tadalafil as medical expulsive therapy for distal ureteral stones: A systematic review and meta-analysis","volume":"49","author":"Belkovsky","year":"2023","journal-title":"Int. Braz. J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.4236\/oju.2020.105017","article-title":"Medical Expulsive Therapy (MET) for Large Distal Ureteral Stones: A Prospective Study Comparing Three Drugs","volume":"10","author":"Khereddine","year":"2020","journal-title":"Open J. Urol."},{"key":"ref_12","first-page":"S35","article-title":"The use of alpha-blockers for the treatment of nephrolithiasis","volume":"8","author":"Lipkin","year":"2006","journal-title":"Rev. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"221","DOI":"10.4081\/aiua.2021.2.221","article-title":"A new original nutraceutical formulation ameliorates the effect of Tadalafil on clinical score and cGMP accumulation","volume":"93","author":"Mirone","year":"2021","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Maisto, M., Schiano, E., Luccheo, G., Luccheo, L., Alfieri, E., Piccolo, V., Iannuzzo, F., Di Lorenzo, R., and Tenore, G.C. (2023). Efficacy of a Multicomponent Nutraceutical Formulation for the Prevention and Treatment of Urinary Tract Stones. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098316"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1590\/S1677-55382010000600002","article-title":"Phyllanthus niruri as a promising alternative treatment for nephrolithiasis","volume":"36","author":"Boim","year":"2010","journal-title":"Int. Braz. J. Urol."},{"key":"ref_16","first-page":"67","article-title":"Adjunctive therapy to promote stone passage","volume":"7","author":"Nuss","year":"2005","journal-title":"Rev. Urol."},{"key":"ref_17","first-page":"7","article-title":"Boldine: A narrative review of the bioactive compound with versatile biological and pharmacological potential","volume":"6","author":"Lamba","year":"2024","journal-title":"J. Complement. Integr. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1111\/j.1476-5381.1996.tb16039.x","article-title":"The effect of S-(+)-boldine on the alpha 1-adrenoceptor of the guinea-pig aorta","volume":"119","author":"Moreau","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_19","first-page":"185","article-title":"Urologists\u2019 opinion on treating asymptomatic stones: Would we treat ourselves as we treat our patients? Survey from European Association of Urology, Young Academic Urologists, Endourology and Urolithiasis working party","volume":"7","author":"Tailly","year":"2023","journal-title":"Turk. J. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.aju.2013.02.003","article-title":"Efficacy and safety of tamsulosin vs. alfuzosin as medical expulsive therapy for ureteric stones","volume":"11","author":"Ibrahim","year":"2013","journal-title":"Arab. J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1097\/JU.0000000000000029","article-title":"Tamsulosin as a Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"201","author":"Cui","year":"2019","journal-title":"J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"82","DOI":"10.4111\/icu.2017.58.2.82","article-title":"Efficacy of phosphodiesterase type 5 inhibitors for the treatment of distal ureteral calculi: A systematic review and meta-analysis","volume":"58","year":"2017","journal-title":"Investig. Clin. Urol."},{"key":"ref_23","first-page":"153","article-title":"Evaluation of the efficacy of Phyllanthus niruri standardized extract combined with magnesium and vitamin B6 for the treatment of patients with uncomplicated nephrolithiasis","volume":"92","author":"Cealan","year":"2019","journal-title":"Med. Pharm. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1046\/j.1464-410X.2002.02794.x","article-title":"The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation","volume":"89","author":"Freitas","year":"2002","journal-title":"BJU Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.juro.2006.04.010","article-title":"Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study","volume":"176","author":"Micali","year":"2006","journal-title":"J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1590\/s1677-5538.ibju.2017.0521","article-title":"Effect of phyllanthus niruri on metabolic parameters of patients with kidney stone: A perspective for disease prevention","volume":"44","author":"Pucci","year":"2018","journal-title":"Int. Braz. J. Urol."},{"key":"ref_27","first-page":"4560607","article-title":"Boldine, an Alkaloid from Peumus boldus Molina, Induces Endothelium-Dependent Vasodilation in the Perfused Rat Kidney: Involvement of Nitric Oxide and Small-Conductance Ca2+-Activated K+ Channel","volume":"2022","author":"Steimbach","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4196\/kjpp.2011.15.1.37","article-title":"Spontaneous contractions augmented by cholinergic and adrenergic systems in the human ureter","volume":"15","author":"Lee","year":"2011","journal-title":"Korean J. Physiol Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/bcpt.13613","article-title":"Current and emerging pharmacological targets for medical expulsive therapy","volume":"130","author":"Lim","year":"2022","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"762.e13","DOI":"10.1016\/j.urology.2010.09.034","article-title":"Characterization of \u03b11-adrenoceptor subtypes mediating contraction in human isolated ureters","volume":"77","author":"Sasaki","year":"2011","journal-title":"Urology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/(SICI)1098-1128(199807)18:4<225::AID-MED2>3.0.CO;2-X","article-title":"A review of the plants of the genus Phyllanthus: Their chemistry, pharmacology, and therapeutic potential","volume":"18","author":"Calixto","year":"1998","journal-title":"Med. Res. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/S0024-3205(99)00052-1","article-title":"Halogenated derivatives of boldine with high selectivity for \u03b11A-adrenoceptors in rat cerebral cortex","volume":"64","author":"Martinez","year":"1999","journal-title":"Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100345","DOI":"10.1016\/j.hermed.2020.100345","article-title":"The possible litholytic effect of Ononis spinosa L. on various human kidney stones\u2014An in vitro experimental evaluation","volume":"22","author":"Bashan","year":"2020","journal-title":"J. Herb. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.fitote.2018.08.013","article-title":"Isoflavonoids with inhibiting effects on human hyaluronidase-1 and norneolignan clitorienolactone B from Ononis spinosa L. root extract","volume":"130","author":"Addotey","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Spiegler, V., Gierlikowska, B., Saenger, T., Addotey, J.N., Sendker, J., Jose, J., Kiss, A.K., and Hensel, A. (2020). Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00889"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:49:09Z","timestamp":1760111349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["medicina60091455"],"URL":"https:\/\/doi.org\/10.3390\/medicina60091455","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]}}}