{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T22:18:45Z","timestamp":1775168325033,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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"],"award-info":[{"award-number":["71\/700.135\/2018"]}],"id":[{"id":"10.13039\/501100005672","id-type":"DOI","asserted-by":"crossref"}]},{"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":["83\/013.186\/2023"],"award-info":[{"award-number":["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\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["150258\/2023-2"],"award-info":[{"award-number":["150258\/2023-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordenadoria 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":["Molecules"],"abstract":"<jats:p>This study aimed to elucidate the vasorelaxant mechanism of action for apigenin 7-glucoside (A7G) by integrating computational and ex vivo pharmacological approaches. Molecular docking simulations were conducted to predict the binding affinities and interactions of A7G with key vascular proteins, specifically human endothelial nitric oxide synthase (eNOS-PDB ID: 1M9M), and human intermediate (IKCa-PDB ID: 9ED1) and small-conductance (SKCa-PDB ID: 6CNN) Ca2+-activated K+ channels. The vasodilatory properties of A7G were subsequently evaluated in isolated mesenteric vascular beds (MVBs) from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). The in silico analysis indicated that A7G possesses favorable binding affinities for the 1M9M, 9ED1, and 6CNN protein targets. Pharmacological assessments demonstrated that A7G induced a dose- and endothelium-dependent reduction in perfusion pressure in MVBs from WKY and SHR rats. The vasodilatory response to A7G was completely abrogated by perfusion with a high-potassium solution or a non-selective K+ channel blocker. Furthermore, co-administration of apamin and TRAM-34, selective inhibitors of SKCa and IKCa, respectively, also abolished the vasorelaxant effects of A7G. Collectively, these findings suggest that the vascular effects of A7G in both WKY and SHR rats involve an endothelium-dependent mechanism, likely initiated by the activation of the NO\/cGMP pathway, which culminates in the opening of IKCa and SKCa channels.<\/jats:p>","DOI":"10.3390\/molecules30214265","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:18:42Z","timestamp":1762186722000},"page":"4265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of the NO\/cGMP Pathway and SKCa and IKCa Channels in the Vasodilatory Effect of Apigenin 7-Glucoside"],"prefix":"10.3390","volume":"30","author":[{"given":"Maria Luiza Fidelis","family":"da Silva","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-0183","authenticated-orcid":false,"given":"Erdi Can","family":"Aytar","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Department of Horticulture, Usak University, 64200 U\u015fak, T\u00fcrkiye"}],"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":"Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1002\/clc.23898","article-title":"Adherence with cardiovascular medications and the outcomes in patients with coronary arterial disease: \u201cReal-world\u201d evidence","volume":"45","author":"Chen","year":"2022","journal-title":"Clin. 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Molecules, 30.","DOI":"10.3390\/molecules30132867"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/21\/4265\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T05:42:18Z","timestamp":1762234938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/21\/4265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":36,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["molecules30214265"],"URL":"https:\/\/doi.org\/10.3390\/molecules30214265","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}