{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:07:44Z","timestamp":1788469664565,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian National Council for Scientific and Technological Development","award":["313047\/2020-0"],"award-info":[{"award-number":["313047\/2020-0"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["308929\/2021-7"],"award-info":[{"award-number":["308929\/2021-7"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["201103\/2022-2"],"award-info":[{"award-number":["201103\/2022-2"]}]},{"name":"Brazilian National Council for Scientific and Technological Development","award":["402101\/2022-7"],"award-info":[{"award-number":["402101\/2022-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Piper amalago L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from P. amalago. The gas chromatography-mass spectrometry analyses identified 47 compounds in the VO, with \u03b2-cyclogermacrene, spathulenol, \u03b2-phellandrene, and \u03b1-pinene standing out. Among the 47 compounds also found in AE and HE by liquid chromatography-mass spectrometry, glycosylated flavones, organic acids, amino acids, and amides were highlighted. Some examples of these compounds are methoxy-methylenedioxy cis-cinnamoyl pyrrolidine, methoxy-methylenedioxy trans-cinnamoyl pyrrolidine, and cyclobutene-2,4-bis-(1,3-benzodioxol-5-methoxy-6-yl)-1,3-dicarboxapyrrolidide. The acute toxicity experiments were conducted on female rats (n = 5). The cardiorenal assays (n = 8) and evaluations of vasodilatory effects on the mesenteric vascular bed (n = 5) were conducted on male rats. In either extract or VO, there were no mortality or changes in relative weights or histopathological analysis of the organs. Urinary volume and renal electrolyte excretion were elevated significantly during repeated dose 7-day treatment with different preparations from P. amalago. None of the preparations induced hypotension or changes in cardiac electrical activity. Only HE promoted significant vasodilatory effects in rats\u2019 isolated mesenteric vascular beds. These effects were completely abolished in the presence of L-NAME plus 4-aminopyridine. Therefore, P. amalago leaves are safe and present diuretic activity after acute and repeated dose administration over 7 days. Moreover, the HE induced significant vasodilator response in rats\u2019 mesenteric vascular beds by NO\/cGMP pathway and voltage-dependent K+ channels activation.<\/jats:p>","DOI":"10.3390\/ph16111630","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T10:32:32Z","timestamp":1700476352000},"page":"1630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Cardiorenal Effects of Piper amalago Are Mediated by the Nitric Oxide\/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels"],"prefix":"10.3390","volume":"16","author":[{"given":"Luciane M.","family":"Monteiro","sequence":"first","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lislaine M.","family":"Klider","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline A. M.","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9934-4027","authenticated-orcid":false,"given":"Paulo V.","family":"Farago","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, Brazil"},{"name":"National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana\u00edna","family":"Emiliano","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), University of Mato Grosso do Sul (UFMS), Campo Grande 79080-190, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roosevelt I. C.","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariany C.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L. P.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"School of Health, Environment, Sustainability and Humanity, Uninter International University Center, Curitiba 80020-110, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"Natural Products Utilization Research Unit, Agricultural Research Service, United States Department of Agriculture, University of Mississippi, University, MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadla S.","family":"Cassemiro","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), University of Mato Grosso do Sul (UFMS), Campo Grande 79080-190, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-2756","authenticated-orcid":false,"given":"Denise B.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), University of Mato Grosso do Sul (UFMS), Campo Grande 79080-190, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5464-4643","authenticated-orcid":false,"given":"Ikhlas A.","family":"Khan","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-5098","authenticated-orcid":false,"given":"Arquimedes","family":"Gasparotto Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados 79825-070, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-2253","authenticated-orcid":false,"given":"Jane","family":"Manfron","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa 84030-900, PR, Brazil"},{"name":"National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.bjp.2015.03.001","article-title":"Anatomical investigations of Piper amalago (jaborandi-manso) for the quality control","volume":"25","author":"Santos","year":"2015","journal-title":"Rev. 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