{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T03:43:16Z","timestamp":1767930196437,"version":"3.49.0"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"01","funder":[{"DOI":"10.13039\/501100005672","name":"Funda\u00e7\u00e3o de Apoio ao Desenvolvimento do Ensino, Ci\u00eancia e Tecnologia do Estado de Mato Grosso do Sul","doi-asserted-by":"crossref","award":["71\/700.135\/2018 and 83\/013.186\/2023"],"award-info":[{"award-number":["71\/700.135\/2018 and 83\/013.186\/2023"]}],"id":[{"id":"10.13039\/501100005672","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["407685\/2018-9"],"award-info":[{"award-number":["407685\/2018-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cardiovascular diseases are the leading causes of deaths worldwide. Complementary therapies, such as medicinal plants, have become increasingly common among treatment options. We propose to investigate the cardioprotective effects of the ethanol-soluble fraction obtained from the aerial parts of Baccharis milleflora in hypertensive rats. Cladodes of B. milleflora were collected, and the aqueous extract was obtained by infusion. The infusion was then treated with ethanol, resulting in the ethanol-soluble fraction of B. milleflora, which was analyzed by LC-DAD-MS. The MS and MS\/MS data obtained from the ethanol-soluble fraction of B. milleflora was submitted to the Global Natural Products Social Molecular Networking platform to generate the molecular network, and three main clusters were detected. Wistar-Kyoto and spontaneously hypertensive rats were divided into different experimental groups, including na\u00efve, control (vehicle), hydrochlorothiazide\n          (25\u2009mg\/kg), and ethanol-soluble fraction of B. milleflora (30, 100, and 300\u2009mg\/kg). The treatment lasted for 28 days. At the end of the treatment, the animals underwent evaluation of renal function, electrocardiographic profile, blood pressure, mesenteric vascular reactivity, serum biochemical parameters, and histopathological analysis. The molecular pathways involved in pharmacological activity were also investigated. After 28 days, animals treated with ethanol-soluble fraction of B. milleflora 30\u2009mg\/kg showed a significant antioxidant, diuretic, and antihypertensive response, as well as reversed endothelial dysfunction and left ventricular hypertrophy induced by hypertension. Treatment with a non-selective NO synthase inhibitor, cGMP inhibitor, or non-selective K+ channel blocker suppressed the antihypertensive effects of ethanol-soluble fraction of B. milleflora. Our findings showed that B. milleflora is a species with cardioprotective activity\n          when administered for a prolonged period to hypertensive rats.<\/jats:p>","DOI":"10.1055\/a-2686-6580","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T23:32:28Z","timestamp":1761780748000},"page":"43-57","source":"Crossref","is-referenced-by-count":0,"title":["Involvement of the NO-cGMP-K Channels Pathway in Cardioprotective Effects of Baccharis milleflora in Hypertensive Rats"],"prefix":"10.1055","volume":"92","author":[{"given":"Lislaine Maria","family":"Klider","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmacology (UFPR), Federal University of Paran\u00e1, Curitiba, PR, Brazil"},{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"},{"name":"Department of Pharmaceutical Sciences, State University of Ponta Grossa, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Aparecida Macedo","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karyne Garcia Tafarelo","family":"Moreno","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Pereira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luana Ale","family":"Bertoncello","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciane Barbosa","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariany Carvalho","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katyuce de Souza","family":"Farias","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), Federal University of Mato Grosso Do Sul, Campo Grande, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline de Moura","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), Federal University of Mato Grosso Do Sul, Campo Grande, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-2756","authenticated-orcid":false,"given":"Denise Brentan","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products and Mass Spectrometry (LaPNEM), Faculty of Pharmaceutical Sciences, Food and Nutrition (FACFAN), Federal University of Mato Grosso Do Sul, Campo Grande, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Manfron","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, State University of Ponta Grossa, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-5098","authenticated-orcid":false,"given":"Arquimedes","family":"Gasparotto Junior","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmacology (UFPR), Federal University of Paran\u00e1, Curitiba, PR, Brazil"},{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","article-title":"The global burden of cardiovascular diseases and risk: A compass for future health","volume":"80","author":"M Vaduganathan","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1161\/HYPERTENSIONAHA.119.14240","article-title":"High blood pressure and cardiovascular disease","volume":"75","author":"F D Fuchs","year":"2020","journal-title":"Hypertension"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1161\/HYPERTENSIONAHA.120.15761","article-title":"Association of cardiovascular risk factors and lifestyle behaviors with hypertension: A mendelian randomization study","volume":"76","author":"S Van-Oort","year":"2020","journal-title":"Hypertension"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.3390\/nu11091970","article-title":"Sodium intake and hypertension","volume":"11","author":"A Grillo","year":"2019","journal-title":"Nutrients"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11906-019-0923-1","article-title":"Emerging therapy in hypertension","volume":"21","author":"M H Stewart","year":"2019","journal-title":"Curr Hypertens Rep"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fphar.2020.00422","article-title":"Herbal medicine for cardiovascular diseases: Efficacy, mechanisms, and safety","volume":"11","author":"A Shaito","year":"2020","journal-title":"Front Pharmacol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1590\/2175-7860200960411","article-title":"Baccharis sect. Caulopterae (Asteraceae, Astereae) no Rio Grande do Sul, Brasil","volume":"60","author":"G Heiden","year":"2009","journal-title":"Rodrigu\u00e9sia"},{"key":"ref8","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-83511-8_9","volume-title":"Morpho-anatomical Characteristics of Species of Baccharis","author":"J Manfron","year":"2021"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.indcrop.2017.12.040","article-title":"Morphoanatomy and essential oil analysis of Baccharis trimera (Less.) DC.(Asteraceae) from Uruguay","volume":"112","author":"M Minteguiaga","year":"2018","journal-title":"Ind Crops Prod"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and community curation of mass spectrometry data with global natural products social molecular networking","volume":"34","author":"M Wang","year":"2016","journal-title":"Nat Biotechnol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"3821","DOI":"10.1021\/jf050046h","article-title":"Discriminating between the six isomers of dicaffeoylquinic acid by LC-MSn","volume":"53","author":"M N Clifford","year":"2005","journal-title":"J Agric Food Chem"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2900","DOI":"10.1021\/jf026187q","article-title":"Hierarchical scheme for LC-MSn identification of chlorogenic acids","volume":"51","author":"M N Clifford","year":"2003","journal-title":"J Agric Food Chem"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"756","DOI":"10.3389\/fphar.2018.00756","article-title":"Bioactive phenolics of the genus Artemisia (Asteraceae): HPLC-DAD-ESI-TQ-MS\/MS profile of the Siberian species and their inhibitory potential against \u03b1-amylase and \u03b1-glucosidase","volume":"9","author":"D N Olennikov","year":"2018","journal-title":"Front Pharmacol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13020-021-00484-5","article-title":"Establishing a genomic database for the medicinal plants in the Brazilian pharmacopoeia","volume":"16","author":"G R Zhou","year":"2021","journal-title":"Chin Med"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1590\/2175-7860200960411","article-title":"Baccharis sect. Caulopterae (Asteraceae, Astereae) no Rio Grande do Sul, Brasil","volume":"60","author":"G Heiden","year":"2009","journal-title":"Rodrigu\u00e9sia"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1089\/jmf.2019.0165","article-title":"Baccharis trimera (Less.) DC: An innovative cardioprotective herbal medicine against multiple risk factors for cardiovascular disease","volume":"23","author":"M MQ Souza","year":"2020","journal-title":"J Med Food"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"410","DOI":"10.4103\/pr.pr_54_19","article-title":"Carqueja (Baccharis trimera) essential oil chronic treatment induces ventricular repolarization disorder in healthy rats but not in type 2 diabetic rats","volume":"11","author":"A P Duque","year":"2019","journal-title":"Pharmacognosy Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/1071576031000076259","article-title":"Antioxidant activity of Baccharis articulata extracts: isolation of a new compound with antioxidant activity","volume":"37","author":"S Q Oliveira","year":"2009","journal-title":"Free Radic Res"},{"key":"ref19","first-page":"516","article-title":"Brazilian Guidelines of Hypertension \u2013 2020","volume":"116","author":"W KS Barroso","year":"2021","journal-title":"Arq Bras Cardiol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.hfc.2019.09.001","article-title":"Hypertension and heart failure: Prevention, targets, and treatment","volume":"16","author":"K E Palo","year":"2020","journal-title":"Heart Fail Clin"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"14489","DOI":"10.3390\/ijms232214489","article-title":"Essential hypertension and oxidative stress: Novel future perspectives","volume":"23","author":"C Franco","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40001-022-00983-7","article-title":"Obesity difference on association blood malondialdehyde level and diastolic hypertension in the elderly population: A cross-sectional analysis","volume":"28","author":"Y Huang","year":"2023","journal-title":"Eur J Med Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"717740","DOI":"10.3389\/fnut.2021.717740","article-title":"Lipid oxidation products on inflammation-mediated hypertension and atherosclerosis: A mini review","volume":"8","author":"X F Leong","year":"2021","journal-title":"Front Nutr"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.plaphy.2020.01.006","article-title":"The effect of developmental and environmental factors on secondary metabolites in medicinal plants","volume":"148","author":"Y Li","year":"2020","journal-title":"Plant Physiol Biochem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.bjp.2014.11.003","article-title":"Morpho-anatomical characteristics of Baccharis glaziovii in support of its pharmacobotany","volume":"24","author":"V C Jasinski","year":"2014","journal-title":"Rev Bras Farmacogn"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1590\/S1984-82502009000100009","article-title":"An\u00e1lise morfoanat\u00f4mica comparativa de duas esp\u00e9cies de carqueja: Baccharis microcephala DC. e B. trimera (Less.) DC., Asteraceae","volume":"45","author":"J M Budel","year":"2009","journal-title":"Braz J Pharm Sci"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bjp.2015.07.007","article-title":"Pharmacobotanical study of Baccharis pentaptera","volume":"25","author":"J M Budel","year":"2015","journal-title":"Rev Bras Farmacogn"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"5741198","DOI":"10.1155\/2022\/5741198","article-title":"Prevention and treatment of cardiovascular diseases with plant phytochemicals: A Review","volume":"2022","author":"R K Bachheti","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"111017","DOI":"10.1016\/j.biopha.2020.111017","article-title":"Myricetin: A review of the most recent research","volume":"134","author":"X Song","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1080\/10408398.2021.1971153","article-title":"Harnessing polyphenol power by targeting eNOS for vascular diseases","volume":"63","author":"M Das","year":"2023","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1038\/s41598-023-29799-z","article-title":"Investigations on the morpho-anatomy and histochemistry of the European mistletoe: Viscum album L. subsp. album","volume":"13","author":"V P Almeida","year":"2023","journal-title":"Sci Rep"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1089\/jmf.2022.0027","article-title":"Evidence of the cardioprotective effects of Aloysia polystachya in isoproterenol-induced myocardial infarction in rats","volume":"26","author":"K GT Moreno","year":"2023","journal-title":"J Med Food"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.jep.2009.01.021","article-title":"Natriuretic and diuretic effects of Tropaeolum majus (Tropaeolaceae) in rats","volume":"122","author":"A Gasparotto jr.","year":"2009","journal-title":"J Ethnopharmacol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jep.2010.12.026","article-title":"Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: Evidence for the inhibition of angiotensin converting enzyme","volume":"134","author":"A Gasparotto jr.","year":"2011","journal-title":"J Ethnopharmacol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1161\/01.HYP.7.2.244","article-title":"An improved fluorometric assay of rat serum and plasma converting enzyme","volume":"7","author":"R A Santos","year":"1985","journal-title":"Hypertension"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/335164a0","article-title":"Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat","volume":"335","author":"H Kawasaki","year":"1998","journal-title":"Nature"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1152\/ajpheart.1991.261.3.H683","article-title":"NPY modulates neurotransmission of CGRP-containing vasodilator nerves in rat mesenteric arteries","volume":"61","author":"H Kawasaki","year":"1991","journal-title":"Am J Physiol Heart Circ Physiol"}],"container-title":["Planta Medica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2686-6580.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T23:33:42Z","timestamp":1767915222000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2686-6580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":37,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2026,1,8]]},"published-print":{"date-parts":[[2026,1]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2686-6580","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0032-0943","1439-0221"],"issn-type":[{"value":"0032-0943","type":"print"},{"value":"1439-0221","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}