{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T22:16:52Z","timestamp":1776118612964,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004944","name":"Naresuan University","doi-asserted-by":"crossref","award":["R2566B040"],"award-info":[{"award-number":["R2566B040"]}],"id":[{"id":"10.13039\/501100004944","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NSRF","award":["B13F670054"],"award-info":[{"award-number":["B13F670054"]}]},{"DOI":"10.13039\/501100014795","name":"Center of Excellence for Innovation in Chemistry","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014795","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Higher Education, Science, Research and Innovation"},{"name":"Global and frontier research university fund, Naresuan University, Thailand","award":["R2566C053"],"award-info":[{"award-number":["R2566C053"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Enhancing endothelial nitric oxide (NO) bioavailability through natural products may provide a promising strategy for the prevention and management of hypertension. This study investigated the phytochemical composition of ethanolic lotus (Nelumbo nucifera) seed extract (LSE), its vasorelaxant mechanisms, effects on endothelial NO production, and antihypertensive activity. Methods: LSE was characterized via LC-ESI-QTOF-MS using accurate mass data and fragmentation patterns. Vasorelaxant effects were evaluated in isolated rat aortas, and the underlying mechanisms were explored using pharmacological inhibitors. NO production was assessed in human endothelial EA.hy926 cells. Hypotensive activity was examined in normotensive rats following intravenous administration of LSE (10, 30, and 100 mg\/kg). Molecular docking was performed to analyze interactions between LSE bioactive compounds and endothelial nitric oxide synthase (eNOS). Results: LC-ESI-QTOF-MS analysis identified 114 compounds, including primary and secondary metabolites. LSE induced vasorelaxation in endothelium-intact aortas, which was reduced by endothelium removal (p &lt; 0.001) and by L-NAME (p &lt; 0.001). LSE also inhibited receptor-operated, Ca2+ channel-mediated vasoconstriction (p &lt; 0.05). In vivo, LSE decreased blood pressure in a dose-dependent manner. In EA.hy926 cells, LSE (750 and 1000 \u00b5g\/mL) increased NO production, an effect attenuated by L-NAME. Molecular docking showed that LSE alkaloids, including nelumborine, nelumboferine, neferine, and isoliensinine had strong affinities for binding with eNOS at the tetrahydrobiopterin (BH4) binding site. Nelumborine exhibited the highest affinity, suggesting its potential as an eNOS modulator. Conclusions: LSE promotes vasorelaxation through the stimulation of endothelium-derived NO release and Ca2+ influx inhibition, contributing to blood pressure reduction. These findings support LSE as a potential natural antihypertensive supplement.<\/jats:p>","DOI":"10.3390\/ph18101500","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T08:10:51Z","timestamp":1759738251000},"page":"1500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vasorelaxant and Hypotensive Mechanisms of Nelumbo\u00a0nucifera Seed Extract: Roles of Nitric Oxide, Calcium Channel Blockade and eNOS Interaction with Active Compounds"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0858-5694","authenticated-orcid":false,"given":"Usana","family":"Chatturong","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitra","family":"Nuengchamnong","sequence":"additional","affiliation":[{"name":"Science Laboratory Centre, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-4873","authenticated-orcid":false,"given":"Anjaree","family":"Inchan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Ministry of Public Health, Praboromarajchanok Institute, Nonthaburi 11000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kittiwoot","family":"To-On","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tippaporn","family":"Bualeong","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-794X","authenticated-orcid":false,"given":"Wiriyaporn","family":"Sumsakul","sequence":"additional","affiliation":[{"name":"Expert Center of Innovative Herbal Products, Thailand Institute of Scientific and Technological Research, Pathum Thani 12120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7601-3332","authenticated-orcid":false,"given":"Anyapat","family":"Atipimonpat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kittiphum","family":"Meekarn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-6007","authenticated-orcid":false,"given":"Yasuteru","family":"Shigeta","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kowit","family":"Hengphasatporn","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4940-7103","authenticated-orcid":false,"given":"Sarawut","family":"Kumphune","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Institute, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Biomedical Engineering and Innovation Research Center, Chiang Mai University, Mueang Chiang Mai District, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6973-158X","authenticated-orcid":false,"given":"Krongkarn","family":"Chootip","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1097\/HJH.0000000000003480","article-title":"2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)","volume":"41","author":"Mancia","year":"2023","journal-title":"J. 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