{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:24Z","timestamp":1787029224449,"version":"build-2736575974"},"reference-count":23,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission ERDF\/FEDER Operational Programme of Murcia","award":["No. 50463"],"award-info":[{"award-number":["No. 50463"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: Numerous epidemiological studies have demonstrated that consuming foods rich in polyphenols and flavonoids can have beneficial effects on various diseases, including arterial hypertension (HTN). Recent research from our laboratory has shown that certain flavonoids exhibit antihypertensive properties in several animal models of HTN. Our objective was to evaluate the effect of Morus alba L. (white mulberry) extracts in an experimental HTN model characterized by nitric oxide (NO) deficiency. Methods: Male Sprague-Dawley rats were divided into four groups: a control group, hypertensive rats treated with an NO synthesis inhibitor (L-NAME) in drinking water for six weeks, L-NAME rats treated with Morus alba L. extract, and L-NAME rats treated simultaneously with captopril. After six weeks of treatment, we measured blood pressure, endothelial vascular function in the aorta, and platelet aggregation function. Results: Morus alba L. extract partially prevented the development of arterial hypertension due to NO deficiency, although it did not completely normalize blood pressure as captopril did. The extract reduced the excessive vasoconstrictor response to phenylephrine in aortic rings and improved vasodilation in response to acetylcholine, with both effects dependent on increased NO production. Morus alba L. extract also reduced the increased platelet aggregation in response to ADP and collagen in hypertensive animals, although it did not fully normalize this function. Conclusions: Morus alba L. extract demonstrates antihypertensive effects, improves vascular reactivity, and reduces platelet aggregation in a model of arterial hypertension. These effects are primarily related to an increase in nitric oxide activity.<\/jats:p>","DOI":"10.3390\/nu17010049","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T04:30:58Z","timestamp":1735273858000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of the Effects of Mulberry Leaf Extracts Morus alba L. on Cardiovascular, Renal, and Platelet Function in Experimental Arterial Hypertension"],"prefix":"10.3390","volume":"17","author":[{"given":"Masoud Akbari","family":"Aghdam","sequence":"first","affiliation":[{"name":"Departamento Fisiolog\u00eda, Facultad Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3390-794X","authenticated-orcid":false,"given":"Ana","family":"Pag\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento Fisiolog\u00eda, Facultad Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7243-0240","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Garc\u00eda-Esta\u00f1","sequence":"additional","affiliation":[{"name":"Departamento Fisiolog\u00eda, Facultad Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-3270","authenticated-orcid":false,"given":"Noem\u00ed M.","family":"Atucha","sequence":"additional","affiliation":[{"name":"Departamento Fisiolog\u00eda, Facultad Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev-nutr-010510-103954","article-title":"The effect of nutrition on blood pressure","volume":"30","author":"Savica","year":"2010","journal-title":"Annu. Rev. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1001\/jama.2016.19043","article-title":"Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990\u20132015","volume":"317","author":"Forouzanfar","year":"2017","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/HJH.0000000000003563","article-title":"Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension","volume":"42","author":"Charchar","year":"2024","journal-title":"J. Hypertens."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta7310","article-title":"Lowering blood pressure to prevent myocardial infarction and stroke: A new preventive strategy","volume":"7","author":"Law","year":"2003","journal-title":"Health Technol. Assess."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/biof.5520120122","article-title":"Bioactive peptides derived from food proteins preventing lifestyle related diseases","volume":"12","author":"Yoshikawa","year":"2000","journal-title":"Biofactors"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1016\/j.lfs.2005.10.010","article-title":"Hypolipidemic and antioxidant effects of Morus alba L. (Egyptian mulberry) root bark fractions supplementation in cholesterol-fed rats","volume":"78","author":"Singab","year":"2006","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.bbrc.2007.04.170","article-title":"Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice","volume":"358","author":"Harauma","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7605","DOI":"10.1021\/jf9014697","article-title":"Effects of mulberry (Morus alba L.) extracts on lipid homeostasis in vitro and in vivo","volume":"57","author":"Liu","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.nutres.2009.06.002","article-title":"Mulberry leaf extract restores arterial pressure in streptozotocin-induced chronic diabetic rats","volume":"29","author":"Naowaboot","year":"2009","journal-title":"Nutr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.fct.2010.11.045","article-title":"Antioxidant and antityrosinase activity of mulberry (Morus alba L.) twigs and root bark","volume":"49","author":"Chang","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1016\/j.foodchem.2011.11.143","article-title":"Antihypertensive effect of mulberry leaf aqueous extract containing \u03b3-aminobutyric acid in spontaneously hypertensive rats","volume":"132","author":"Yang","year":"2012","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106029","DOI":"10.1016\/j.phrs.2021.106029","article-title":"Mulberry leaf (Morus alba L.): A review of its potential influences in mechanisms of action on metabolic diseases","volume":"175","author":"Zhang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_13","first-page":"54","article-title":"Cardioprotective and antihypertensive potential of Morus alba L. in isoproterenol-induced myocardial infarction and renal artery ligation-induced hypertension","volume":"13","author":"Nade","year":"2013","journal-title":"J. Nat. Remedies"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3390\/nu10040484","article-title":"Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L-NAME Hypertensive Rats","volume":"10","author":"Paredes","year":"2018","journal-title":"Nutrients"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.3390\/nu10081107","article-title":"Moderate Effect of Flavonoids on Vascular and Renal Function in Spontaneously Hypertensive Rats","volume":"10","author":"Paredes","year":"2018","journal-title":"Nutrients"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Leyva-Jim\u00e9nez, F.J., Ruiz-Malag\u00f3n, A.J., Molina-Tijeras, J.A., Diez-Echave, P., Vezza, T., Hidalgo-Garc\u00eda, L., Lozano-S\u00e1nchez, J., Arr\u00e1ez-Rom\u00e1n, D., Cenis, J.L., and Lozano-P\u00e9rez, A.A. (2020). Comparative Study of the Antioxidant and Anti-Inflammatory Effects of Leaf Extracts from Four Different Morus alba Genotypes in High Fat Diet-Induced Obesity in Mice. Antioxidants, 9.","DOI":"10.3390\/antiox9080733"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Akbari Aghdam, M., Romec\u00edn, P., Garc\u00eda-Esta\u00f1, J., and Atucha, N.M. (2023). Role of Nitric Oxide in the Altered Calcium Homeostasis of Platelets from Rats with Biliary Cirrhosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310948"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1253\/jcj.41.259","article-title":"Pathogenesis of spontaneous hypertension as a model for essential hypertension","volume":"41","author":"Yamori","year":"1977","journal-title":"Jpn. Circ. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11906-009-0083-9","article-title":"Recent advances in genetics of the spontaneously hypertensive rat","volume":"12","author":"Pravenec","year":"2010","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3390\/pathophysiology27010007","article-title":"Chronic L-Name-Treatment Produces Hypertension by Different Mechanisms in Peripheral Tissues and Brain: Role of Central eNOS","volume":"27","author":"Pechanova","year":"2020","journal-title":"Pathophysiology"},{"key":"ref_21","first-page":"317","article-title":"Restriction of nitric oxide rather than elevated blood pressure is responsible for alterations of vascular responses in nitric oxide-deficient hypertension","volume":"45","year":"1996","journal-title":"Physiol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1002\/mnfr.201600233","article-title":"Morus alba extract modulates blood pressure homeostasis through eNOS signaling","volume":"60","author":"Carrizzo","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1080\/10641963.2018.1469645","article-title":"Effects of an ethanolic extract of mulberry fruit on blood pressure and vascular remodeling in spontaneous hypertensive rats","volume":"41","author":"Park","year":"2019","journal-title":"Clin. Exp. Hypertens."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/1\/49\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:01:12Z","timestamp":1760115672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/1\/49"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,27]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["nu17010049"],"URL":"https:\/\/doi.org\/10.3390\/nu17010049","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,27]]}}}