{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:05:56Z","timestamp":1789031156527,"version":"build-2803163510"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders. Micronized purified flavonoid fraction (MPFF, commercial Daflon 1000\u00a0mg) is a preparation that contains mainly diosmin and a small fraction of hesperidin. Both active ingredients are flavonoids, known for their anti-inflammatory and antioxidant properties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Whether the MPFF can alter hemodynamic behavior was examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Daflon 1,000\u00a0mg was administered for 60\u00a0days, and the hemodynamic parameters were measured during the circadian cycle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no significant differences for systolic blood pressure (100.1 \u00b1 10.6\u00a0mmHg vs. 104.8 \u00b1 7.7\u00a0mmHg) or diastolic blood pressure (73.8 \u00b1 3.1\u00a0mmHg vs. 76.4 \u00b1 6.6\u00a0mmHg) before and after MPFF intake, respectively (p &amp;gt; 0.05). However, in sharp contrast, the heart rate reduced significantly after intake of MPFF (88.8 \u00b1 10.5\u00a0bpm vs. 79.3 \u00b1 9.7\u00a0bpm; p &amp;lt; 0.05). The mean blood pressure was negatively correlated with the heart rate (HR) in the afternoon (r = \u22120.450, p = 0.016). During this period, there was a decrease in vein inflammation and varicosity, as shown by magnetic resonance imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We reported a new effect of MPFF as an attenuator of the heart rate. Because venous insufficiency decreased during the observed drug administration period, further studies are needed to examine whether the ability of diosmin and hesperidin to reduce vein disorders is directly linked to their action on heart rate.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1612315","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T04:10:39Z","timestamp":1755144639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Micronized purified flavonoid fraction [Daflon]-induced bradycardia"],"prefix":"10.3389","volume":"16","author":[{"given":"Jhennyfer Aline Lima","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathas Pereira das","family":"Gra\u00e7as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gledson de Oliveira","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.36660\/abc.20220372","article-title":"Arq bras cardiol","volume":"10","author":"Albricker","year":"2022"},{"key":"B2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/1043-6618(91)90088-f","article-title":"Diosmin therapy alters the in vitro metabolism of noradrenaline by the varicose human saphenous vein","volume":"24","author":"Araujo","year":"1991","journal-title":"Pharmacol. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"516","DOI":"10.36660\/abc.20201238","article-title":"Diretrizes Brasileiras de Hipertens\u00e3o Arterial \u2013 2020","volume":"116","author":"Barroso","year":"2020","journal-title":"Arq. Bras. Cardiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1177\/00033197050560i104","article-title":"Chronic venous insufficiency and the therapeutic effects of daflon 500 mg","volume":"56","author":"Bergan","year":"2005","journal-title":"Angiology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"591","DOI":"10.2147\/VHRM.S324112","article-title":"Is there a difference in the clinical efficacy of diosmin and micronized purified flavonoid fraction for the treatment of chronic venous disorders? Review of available evidence","volume":"16","author":"Cazaubon","year":"2021","journal-title":"Vasc. Health Risk Manag."},{"key":"B6","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2017.11.024","article-title":"Circadian clock-mediated regulation of blood pressure","volume":"1","author":"Douma","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1056\/NEJMra2216709","article-title":"Tricuspid regurgitation","volume":"18","author":"Hahn","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"10760296221121282","DOI":"10.1177\/10760296221121282","article-title":"Association between blood lipid levels and lower extremity deep venous thrombosis: a population-based cohort study","volume":"28","author":"Huang","year":"2022","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.3390\/biomedicines10051076","article-title":"Potential and therapeutic roles of diosmin in human diseases","volume":"6","author":"Huwait","year":"2022","journal-title":"Biomedicines"},{"key":"B10","volume-title":"Qu\u00edmica farmac\u00eautica","author":"Korolkovas","year":"2008"},{"key":"B11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.12820\/rbafs.v.6n2p5-18","article-title":"Question\u00e1rio Internacional de Atividade F\u00edsica (IPAQ): estudo de validade e reprodutibilidade no Brasil","volume":"6","author":"Matsudo","year":"2001","journal-title":"Rev. Bras. Ativ. F\u00eds Sa\u00fade"},{"key":"B12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.2114\/ahs.14.293","article-title":"Calculation of mean arterial pressure during exercise as a function of heart rate","volume":"14","author":"Moran","year":"1995","journal-title":"Appl. Hum. Sci."},{"key":"B13","unstructured":"PubChem compound summary for CID 5281613, diosmin\n          \n          \n          2025"},{"key":"B14","doi-asserted-by":"publisher","first-page":"S33","DOI":"10.1177\/0003319703054001S05","article-title":"From symptoms to leg edema: efficacy of daflon 500 mg","volume":"54","author":"Nicolaides","year":"2003","journal-title":"Angiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1177\/0003319701052001s07","article-title":"Clinical benefits of daflon 500mg in the Most severe stages of chronic venous insufficiency","volume":"52","author":"Ramelet","year":"2001","journal-title":"Angiology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.avsg.2014.10.009","article-title":"Biomolecular mechanisms in varicose veins development","volume":"29","author":"Segiet","year":"2015","journal-title":"Ann. Vasc. Surg."},{"key":"B23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.ejphar.2011.12.040","article-title":"Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats","volume":"679","author":"Silambarasan","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1007\/s11011-025-01615-9","article-title":"Neuroprotective potential of hispidulin and diosmin: a review of molecular mechanisms","volume":"40","author":"Singh","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.smrv.2016.02.003","article-title":"Circadian mechanisms of 24-hour blood pressure regulation and patterning","volume":"33","author":"Smolensky","year":"2017","journal-title":"Sleep. Med. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"720","DOI":"10.36660\/abc.20201047","article-title":"Update of the Brazilian guidelines for valvular heart disease","volume":"115","author":"Tarasoutchi","year":"2020","journal-title":"Arq. Bras. Cardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1542\/peds.2010-2221","article-title":"Hormonal contraception and thrombotic risk: a multidisciplinary approach","volume":"127","author":"Trenor","year":"2011","journal-title":"Pediatrics"},{"key":"B21","article-title":"Deep venous thrombosis","author":"Waheed","year":"2025"},{"key":"B22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/B978-0-444-53491-0.00008-0","article-title":"Regulation of blood pressure by the arterial baroreflex and autonomic nervous system","volume":"117","author":"Wehrwein","year":"2013","journal-title":"Handb. Clin. Neurol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1612315\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T04:10:41Z","timestamp":1755144641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1612315\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":23,"alternative-id":["10.3389\/fphar.2025.1612315"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1612315","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"article-number":"1612315"}}