{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T22:51:39Z","timestamp":1786575099907,"version":"build-2736575974"},"reference-count":14,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Grantov\u00e1 Agentura \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["17-05409S"],"award-info":[{"award-number":["17-05409S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The ministry of education, youth and sport (CZ)","award":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000841"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_019\/0000841"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Quercetin is proven to decrease arterial blood pressure when given orally. Its bioavailability is, however, low and, therefore, its metabolites could rather be responsible for this effect. In particular, the colonic metabolites of quercetin, 3,4-dihydroxyphenylacetic acid (DHPA), 4-methylcatechol (4MC), and 3-(3-hydroxyphenyl)propionic acid (3HPPA), have been previously shown to decrease the blood pressure in spontaneously hypertensive rats (SHR). Interestingly, the mechanisms of action of these three metabolites are different. The aim of this study is hence to investigate if these metabolites can potentiate each other and thus decrease blood pressure in reduced doses. Three double-combinations of previously mentioned metabolites were administered to SHR as infusions to mimic a real biological situation. All combinations significantly decreased the blood pressure in SHR but there were important differences. The effect of DHPA and 4MC was mild and very short. A combination of DHPA with 3HPPA caused more pronounced effects, which were also rather short-lived. The last combination of 3HPPA and 4MC caused a long-lasting effect. In conclusion, certain combinations of quercetin metabolites have a more pronounced antihypertensive effect than single metabolites.<\/jats:p>","DOI":"10.3390\/nu12010213","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T03:20:22Z","timestamp":1579058422000},"page":"213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A Mixture of Phenolic Metabolites of Quercetin Can Decrease Elevated Blood Pressure of Spontaneously Hypertensive Rats Even in Low Doses"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8443-0512","authenticated-orcid":false,"given":"Iveta","family":"Najmanov\u00e1","sequence":"first","affiliation":[{"name":"Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Akademika Heyrovskeho 1203\/8, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0728-4646","authenticated-orcid":false,"given":"Jana","family":"Pourov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Akademika Heyrovskeho 1203\/8, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-6900","authenticated-orcid":false,"given":"P\u0159emysl","family":"Mlad\u011bnka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University, Akademika Heyrovskeho 1203\/8, 500 05 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.phrs.2014.07.005","article-title":"The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: Correlation with beta-glucuronidase activity","volume":"89","author":"Perez","year":"2014","journal-title":"Pharmacol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1093\/jn\/137.11.2405","article-title":"Quercetin reduces blood pressure in hypertensive subjects","volume":"137","author":"Edwards","year":"2007","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/1541-4337.12351","article-title":"The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective","volume":"17","author":"Williamson","year":"2018","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.freeradbiomed.2003.09.022","article-title":"Colonic metabolism of dietary polyphenols: Influence of structure on microbial fermentation products","volume":"36","author":"Rechner","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"De Bruyne, T., Steenput, B., Roth, L., De Meyer, G.R.Y., Santos, C.N.D., Valentova, K., Dambrova, M., and Hermans, N. (2019). Dietary Polyphenols Targeting Arterial Stiffness: Interplay of Contributing Mechanisms and Gut Microbiome-Related Metabolism. Nutrients, 11.","DOI":"10.3390\/nu11030578"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Galindo, P., Rodriguez-Gomez, I., Gonzalez-Manzano, S., Duenas, M., Jimenez, R., Menendez, C., Vargas, F., Tamargo, J., Santos-Buelga, C., and Perez-Vizcaino, F. (2012). Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032673"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/mnfr.201500761","article-title":"Flavonoid metabolite 3-(3-hydroxyphenyl) propionic acid formed by human microflora decreases arterial blood pressure in rats","volume":"60","author":"Najmanova","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.vph.2018.08.008","article-title":"Two flavonoid metabolites, 3,4-dihydroxyphenylacetic acid and 4-methylcatechol, relax arteries ex vivo and decrease blood pressure in vivo","volume":"111","author":"Pourova","year":"2018","journal-title":"Vasc. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.abb.2016.01.014","article-title":"Identification and quantification of novel cranberry-derived plasma and urinary (poly) phenols","volume":"599","author":"Feliciano","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jnutbio.2015.11.007","article-title":"Age related differences in the plasma kinetics of flavanols in rats","volume":"29","author":"Margalef","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.foodchem.2017.03.141","article-title":"Flavanol plasma bioavailability is affected by metabolic syndrome in rats","volume":"231","author":"Margalef","year":"2017","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00394-017-1572-2","article-title":"Measuring the impact of olive pomace enriched biscuits on the gut microbiota and its metabolic activity in mildly hypercholesterolaemic subjects","volume":"58","author":"Conterno","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1900261","DOI":"10.1002\/mnfr.201900261","article-title":"4-Methylcatechol, a Flavonoid Metabolite with Potent Antiplatelet Effects","volume":"63","author":"Applova","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jnutbio.2019.01.001","article-title":"CSRP3 mediates polyphenols-induced cardioprotection in hypertension","volume":"66","author":"Oudot","year":"2019","journal-title":"J. Nutr. Biochem."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/213\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:42:58Z","timestamp":1760362978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/1\/213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,14]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["nu12010213"],"URL":"https:\/\/doi.org\/10.3390\/nu12010213","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,14]]}}}